s-1-(combination) and Neoplasm-Metastasis

This study aimed to compare the efficacy and safety of S-1 and capecitabine in patients with metastatic colorectal carcinoma (mCRC).. Eligible prospective clinical trials were searched and available data were extracted. Odds ratio and hazard ratio of available outcomes including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled for analysis.. A total of 6 studies including 828 patients were included. The results of pooled analysis showed no statistical difference in short-term efficacy including ORR (95% confidence interval [CI]: 0.68-1.19; P = .48) or DCR (95% CI: 0.65-1.29; P = .61), or long-term efficacy including PFS (95% CI: 0.75-1.08; P = .26) or OS (95% CI: 0.78-1.13; P = .50). Symptoms of diarrhea at any grade were more prevalent (95% CI: 1.21-2.29; P = .002) in patients treated with S-1, while hand-foot syndrome (HFS) at any grade (95% CI: 0.24-0.48; P < .0001) or high grade (95% CI: 0.09-0.48; P < .0001) was more frequent in capecitabine group. AEs including leucopenia, neutropenia, anemia, thrombocytopenia, vomiting, oral mucositis, stomatitis, elevated alanine transaminase, or peripheral neuropathy showed no statistical difference between S-1 and capecitabine group (all P > .05).. This meta-analysis reveals that S-1 has comparable efficacy, lower risk of HFS and higher incidence of diarrhea compared to capecitabine for treatment in patients with mCRC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Humans; Neoplasm Metastasis; Oxonic Acid; Proportional Hazards Models; Randomized Controlled Trials as Topic; Survival Analysis; Tegafur

We performed a meta-analysis to evaluate the efficacy and safety for S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.. Eligible randomized clinical trials (RCTs) were included, of which data were extracted by inclusion criteria and exclusion one. Odds ratio and hazard ratio (HR) of outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects (AEs) were explored for the final analysis.. Twenty-one RCTs including 3263 patients were fit into the analysis. Pooled HR for PFS was 1.01 (95% CI: 0.92-1.10; p = 0.88), the pooled HR for OS was 0.95 (95% CI: 0.85-1.06; p = 0.33) and the pooled odds ratio for ORR was 0.74 (95% CI: 0.61-0.90; p = 0.003). S-1-based regimens showed milder AEs in high-grade nausea/vomit, anorexia, leukopenia, neutropenia and febrile neutropenia (all p < 0.05).. The present study has revealed that S-1-based regimens are accompanied by the similar efficacy and slighter AEs compared with standard regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asian People; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Randomized Controlled Trials as Topic; Tegafur; Treatment Outcome

We performed a meta-analysis of S-1-containing regimens versus control in the management of locally advanced/metastatic non-small-cell lung cancer.. Eligible studies included randomized studies evaluating S-1-containing regimens in the settings of locally advanced, first-line metastatic or second-line metastatic non-small-cell lung cancer.. Pooled odds ratio for overall response rate was 1.09 (95% CI: 0.85-1.38; p = 0.2), the pooled hazard ratio for progression-free survival was 0.98 (95% CI: 0.88-1.09; p = 0.69) and the pooled hazard ratio for overall survival was 0.98 (95% CI: 0.88-1.10; p = 0.75) for S-1-based regimens versus control. Moreover, the relative risk of febrile neutropenia was 0.34 (95% CI: 0.20-0.59; p = 0.0001).. Our meta-analysis has demonstrated that S-1-based regimens are associated with similar efficacy outcomes and better hematological tolerability.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Tegafur; Treatment Outcome

S-1 is an oral fluoropyrimidine that consists of tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate. It has been developed as a prodrug of 5-fluorouracil with the goal of improving therapeutic efficacy and tolerability.. This review aims to provide an evidence-based update of clinical trials that have investigated the clinical efficacy, adverse-event profile, dosage and administration of S-1, given alone or in combination with conventional chemotherapeutics and new target-oriented drugs, in the management of colorectal cancer (CRC). Additionally, differences in the tolerability and pharmacokinetics of S-1 between Caucasians and Asians have been described. Finally, the therapeutic efficacy of S-1 regarding metastatic CRC or postoperative CRC has been discussed. Available data have stimulated further research, including Phase III trials for the treatment of advanced CRC.. Treatment using S-1 combined with oxaliplatin (± bevacizumab) and irinotecan has achieved promising results in terms of feasibility, safety and effectiveness. Furthermore, S-1 is an acceptable treatment as adjuvant chemotherapy for colon cancer.

Topics: Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Chemotherapy, Adjuvant; Colon; Colorectal Neoplasms; Drug Combinations; Humans; Irinotecan; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectum; Tegafur

The prognosis for hepatocellular carcinoma with extrahepatic metastasis or vascular invasion is very poor. We treated a case successfully by combining chemotherapy and liver resection for hepatocellular carcinoma with multiple pulmonary metastases and vascular invasion. A 56-year-old man who complained of abdominal pain in his right side was transported to the hospital by ambulance. Because CT scan revealed the rupture of hepatocellular carcinoma, he underwent emergency transcatheter arterial embolization (TAE). A close examination revealed tumor thrombus in the inferior vena cava and posterior segment of the portal vein branch, with multiple pulmonary metastases. We conducted right hepatic lobectomy and removal of the inferior vena cava tumor thrombus. After the operation, pulmonary metastatic lesions gradually grew larger, so the oral administration of S-1 at 120 mg per day was started. At the end of the first course, the CT scan revealed that multiple pulmonary metastases were significantly reduced, and treatment was maintained until the end of 4 courses. A prolongation of survival could be expected by combining systemic chemotherapy and liver resection for advanced hepatocellular carcinoma such as the present case.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Combined Modality Therapy; Drug Combinations; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neovascularization, Pathologic; Oxonic Acid; Prognosis; Tegafur

The effectiveness of systemic chemotherapy for metastatic gastric cancer has already been established. However, a standard chemotherapy still remains uncertain. New agents such as S-1, CPT-11 and taxanes are markedly improving the response rates for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard regimen to treat gastric cancer will be reported. In this article, we described the current state of S-1 +CPT-11 combination chemotherapy for gastric cancer. Among various CPT-11 based chemotherapy, S-1 +CPT-11 appears to be the most effective and less toxic treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Maximum Tolerated Dose; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur

We have previously demonstrated S-1 is non-inferior to taxane with respect to overall survival as first-line chemotherapy for HER2-negative metastatic breast cancer. We aimed to confirm whether S-1 is also non-inferior to anthracycline-containing regimens in the same setting.. We conducted an open-label, non-inferiority, Phase 3 study. Individuals who had HER2-negative metastatic breast cancer, had received no chemotherapy for advanced disease and had endocrine therapy resistance, were randomly assigned to the anthracycline-containing regimens or S-1. The primary endpoint was overall survival. A pre-planned combined analysis of our two Phase 3 studies was also carried out.. We enrolled 230 patients (anthracycline, n = 115; S-1, n = 115). Median overall survival was 30.1 months (95% CI 24.9-35.8) with the S-1 group and 33.7 months (95% CI 25.5-36.9) with the anthracycline group. The HR for the anthracycline group was 1.09 (95% CI 0.80-1.48). The combined analysis constituted 814 patients (395 assigned to standard treatment (anthracycline or taxane); 419 assigned to S-1). Median overall survival was 36.3 months in the standard treatment group and 32.7 months in the S-1 group. S-1 was non-inferior to standard treatment in terms of overall survival (HR 1.06 (95% CI 0.90-1.25); P non-inferiority = 0.0062).. S-1 could be considered a new treatment option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer.. The University Hospital Medical Information Network, Japan: UMIN000005449. This trial was registered on 15 April, 2011.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents, Hormonal; Breast Neoplasms; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Receptor, ErbB-2; Survival Analysis; Taxoids; Tegafur; Treatment Outcome; Young Adult

The TRICOLORE trial previously demonstrated that S-1 and irinotecan plus bevacizumab was non-inferior, based on progression-free survival (PFS), to 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)/capecitabine and oxaliplatin (CapeOX) plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC). Overall survival (OS) data were immature at the time of the primary analysis.. In total, 487 patients from 53 institutions with previously untreated mCRC were randomly assigned (1:1) to receive either mFOLFOX6/CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; 3- or 4-week regimen). The final OS data were analysed from follow-up data collected until 30th September 2017.. With a median follow-up period of 48.7 months, median survival times were 32.6 and 34.3 months (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.72-1.10, P = 0.293) and median PFS durations were 10.8 and 14.0 months in the control and experimental groups, respectively (HR: 0.86, 95% CI: 0.71-1.04, P < 0.0001 for non-inferiority). In patients with left-sided RAS wild-type tumours, median PFS durations were 11.4 and 16.9 months in the control and experimental groups, respectively (HR: 0.68, 95% CI: 0.48-0.96, P = 0.028).. S-1 and irinotecan plus bevacizumab resulted in comparable OS and non-inferior PFS with that of mFOLFOX6/CapeOX plus bevacizumab treatment as first-line chemotherapy for patients with mCRC. We recommend the use of S-1 and irinotecan plus bevacizumab as a standard first-line regimen independent of tumour sidedness or RAS status in mCRC.. UMIN-CTR: 000007834.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Female; Fluorouracil; Genes, ras; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Mutation; Neoplasm Metastasis; Organoplatinum Compounds; Oxonic Acid; Proto-Oncogene Proteins B-raf; Quality of Life; Tegafur

Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer (GC) with peritoneal metastasis (PM). Recently, superiority of IP administration of paclitaxel (PTX) combined with S-1 and intravenous PTX over conventional systemic chemotherapy was suggested in a phase III study, although the difference in overall survival did not reach statistical significance in the primary analysis. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy are warranted. We designed a new regimen combining IP PTX with S-1 plus cisplatin (SP), which is regarded as the standard first-line treatment for metastatic GC in Japan, and subsequently carried out a dose-escalation study.. The combination was a 5-weekly regimen. IP PTX was to be administered on days 1, 8, and 22 with an initial dose of 15 mg/m2 at level 1 and 20 mg/m2 at level 2. S-1 was to be administered orally at a fixed dose of 80 mg/m2 b.i.d. for 21 days followed by a -14-day rest. Cisplatin was to be administered intravenously at a dose of 60 mg/m2 on day 8. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 (G3) febrile neutropenia, G3 thrombocytopenia, and G3 nonhematological toxicity.. A total of 9 patients with macroscopic PM were enrolled. No DLTs were observed among the 3 patients at level 1 and 6 patients at level 2. No adverse events or technical problems associated with the IP administration were observed. Consequently, the maximum-tolerated dose was not reached, and the dose for further clinical trials of IP PTX was determined as 20 mg/m2. As for efficacy, peritoneal lavage cytology turned negative after the first course in 4 of 7 patients who had positive cytology before treatment.. The present study determined the dose for further clinical trials of IP PTX to be 20 mg/m2, when combined with the 5-weekly SP regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Treatment Outcome

Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival following palliative-intent chemotherapy. Sunitinib, everolimus, and pembrolizumab have been proposed as active agents based on previous phase II trials. In this phase II study, TC patients previously treated with platinum-based chemotherapy were enrolled. The patients received S-1 orally twice daily at a dose of 40-60 mg/m

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Palliative Care; Retreatment; Tegafur; Thymus Neoplasms; Treatment Outcome

The upregulation of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important mechanisms of resistance to 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) after long exposure to 5-FU.S-1 (containing a DPD inhibitor) combined with raltitrexed (a TS inhibitor) showed a moderate effect, which needs further study as a third- or later-line therapy in mCRC.. 5-fluorouracil (5-FU) is a fundamental drug in the treatment of metastatic colorectal cancer (mCRC). Patients with mCRC are often exposed to 5-FU and/or its analogues for a long time because of its central role in treatment regimens. The upregulation of dihydropyrimidine dehydrogenase (DPD) and/or thymidylate synthase (TS) are important mechanisms of resistance of 5-FU. To evaluate the efficacy and safety of S-1 (containing a DPD inhibitor) and raltitrexed (a TS inhibitor) for refractory mCRC, a one-center, single-arm, prospective phase II trial was conducted.. Patients who had mCRC that had progressed after treatment with fluoropyrimidine, irinotecan, and oxaliplatin and who had at least one measurable lesion were eligible for this trial. Patients received oral S-1 (80-120 mg for 14 days every 3 weeks) plus an intravenous infusion of raltitrexed (3 mg/m. In total, 46 patients were enrolled. Three patients did not complete the first assessment because of adverse events and unwillingness, leaving tumor response evaluation available in 43 patients. Of 43 evaluable patients, the ORR was 13.9% and disease control rate was 58.1%. In the intention-to-treat population (. S-1 combined with raltitrexed for refractory mCRC showed moderate effect, and it is worthy of further study as third- or later-line therapy in mCRC.

Topics: Adult; Aged; Colorectal Neoplasms; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Quinazolines; Tegafur; Thiophenes

Trastuzumab with S-1 plus cisplatin was proved to be effective for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer with measurable lesions. However, the efficacy and safety of this regimen in the absence of measurable lesions are unknown.. Patients with HER2-positive gastric cancer without measurable lesions received cisplatin plus trastuzumab intravenously on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The primary end-point was overall survival, and 40 patients were planned to be enrolled.. Fifteen patients were enrolled. The median overall survival was 14.4 months. The 1- and 3-year overall survival rates were 66.7 % and 26.7 %, respectively. Major grade 3-4 adverse events included neutropenia (47%), anemia (40%), diarrhea (20%), nausea (20%), and anorexia (20%).. Trastuzumab with S-1 plus cisplatin might be effective and tolerable for HER2-positive advanced gastric cancer without measurable lesions.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome; Young Adult

In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer.. The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed.. This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment.. Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1.. S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.

Topics: Ado-Trastuzumab Emtansine; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Humans; Maytansine; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Receptor, ErbB-2; Tegafur; Trastuzumab; Treatment Outcome

Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer.. Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75-88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7-9.5 months). The median overall survival was 23.1 months (95% CI 17.4-28.8 months). The response rate was 44% (95% CI 30.2-57.8%), and the disease control rate was 88% (95% CI 79.0-97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events.. S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Neoplasm Metastasis; Oxonic Acid; Prognosis; Prospective Studies; Survival Rate; Tegafur

The aim of this study was to investigate the impact of adverse events (AEs) on health utility and health-related quality of life (HRQOL) in patients with metastatic breast cancer undergoing first-line chemotherapy.. We analyzed the data from the SELECT BC study, a multicenter, open-label, randomized, phase III study conducted in Japan, which compared first-line S-1 with taxane therapies. Heath utility and HRQOL were assessed using the EQ-5D-3L and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline and 3, 6, and 12 months after treatment initiation. Health utility was calculated based on societal preferences, and AEs were reported at each cycle of the study treatment. Linear marginal mean models were used to quantify the impact of the last AEs (with 10 or more incidences) observed before HRQOL assessment on health utility and HRQOL.. Analysis included 380 patients and 12 (of 15) AEs. Grade 1 nausea and oral mucositis, grade 1 and 2 edema, and grade 2 fatigue, motor and sensory neuropathy, and myalgia were significantly associated with disutility, measured using the EQ-5D-3L. Grade 1 oral mucositis, grade 1 and 2 fatigue, and grade 2 sensory neuropathy were significantly associated with impaired global health status in the EORTC QLQ-C30. AEs associated with decrements in the five functioning scales included fatigue, oral mucositis, nausea, edema, motor and sensory neuropathy, and myalgia.. We reported disutilities caused by AEs in patients with metastatic breast cancer under chemotherapy. These findings can be applied to future model-based cost-effectiveness analyses.. C000000416.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Drug Combinations; Female; Health Status; Humans; Japan; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Quality of Life; Surveys and Questionnaires; Taxoids; Tegafur; Time Factors

Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.. Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.. In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).. OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Drug Administration Schedule; Drug Combinations; Exome Sequencing; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxaliplatin; Oxonic Acid; Proto-Oncogene Proteins p21(ras); Tegafur; Treatment Outcome; Tumor Suppressor Protein p53

The aim of this single-arm phase II clinical trial was to evaluate whether the alternate-day administration of S-1 plus irinotecan would reduce the incidence of severe diarrhea in comparison to consecutive-day S-1 administration (standard IRIS regimen) in second-line treatment for patients with metastatic colorectal cancer.. A total of 51 patients were enrolled. The incidence of grade ≥ 3 diarrhea was 15.7% (8/51). Other common grade ≥ 3 adverse events were neutropenia, anemia, thrombocytopenia and fatigue were 13.7% (7/51), 5.9% (3/51), 2.0% (1/51) and 5.9% (3/51), respectively. The relative dose intensities of irinotecan, bevacizumab, and S-1 were 80.0, 86.8, and 77.7%, respectively. The median progression-free survival and overall survival were 8.4 months (5.8-9.8) and 17.1 months (11.8-22.3).. The alternate-day S-1 administration does not have significant effectiveness to reduce diarrhea in patients who received second-line treatment for metastatic colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Incidence; Irinotecan; Male; Neoplasm Metastasis; Oxonic Acid; Survival Rate; Tegafur

Chemoradiotherapy using intensity-modulated radiotherapy (IMRT) is expected to provide a powerful alternative to conventional chemotherapy with a low incidence of adverse events. This study evaluated the efficacy of intensity modulated radiotherapy in combination with gemcitabine and S-1 as neoadjuvant chemoradiotherapy (NACRT) for borderline-resectable pancreatic cancer with arterial involvement (BR-A).. A total of 27 patients with BR-A were enrolled in this study between February 2012 and September 2015. IMRT was administered at 50.4 Gy in 28 fractions with concurrent gemcitabine at a dose of 600 mg/m. Only one patient (3.5%) experienced gastrointestinal adverse events at grade 3 or higher. Nineteen patients (70.3%) underwent resection, and R0 resection was achieved in 18 patients (94.7%). Thirteen patients (68.4%) developed distant metastasis at the initial site of recurrence after resection. Local recurrence developed in only one of these patients (7.7%). The median overall survival and 1-year survival rates were 22.4 months and 81.3%, respectively.. Concurrent IMRT with gemcitabine and S-1 for patients is feasible as NACRT for BR-A with low gastrointestinal toxicity. IMRT can be employed as a standard radiotherapy to provide more effective NACRT with powerful chemotherapy drugs.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Arteries; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prospective Studies; Radiotherapy, Intensity-Modulated; Survival Rate; Tegafur; Tomography, X-Ray Computed

This Phase II trial evaluated the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 and oxaliplatin (SOX) plus bevacizumab (Bev) in patients with colorectal liver metastasis (CRLM).. Patients with initially resectable CRLM received four cycles of SOX plus Bev as NAC. We adopted the R0 resection rate as the primary endpoint, and the threshold R0 resection rate was set at 80%.. Between December 2010 and August 2014, 61 patients were enrolled in this study and all started NAC. The completion rate of NAC was 82.0%. Three patients (4.9%) developed severe liver dysfunction caused by NAC and one patient finally decided against resection. Three patients (4.9%) were judged as having progressive disease during or after NAC and did not undergo liver resection. Among 57 patients who underwent liver resection after NAC, three patients were diagnosed with CRLM by pre-treatment imaging modalities and received NAC although a final pathological diagnosis was another malignant disease or benign condition. Finally, 47 of the 54 patients (87.0%) with resected CRLM achieved R0 resection. The pathological complete response rate of the 54 patients was 13.0%, and 31.5% were judged as pathological responders. However, the R0 resection rate of 77.0% in the entire cohort did not meet the endpoint.. NAC with SOX plus Bev has an acceptable toxicity profile and achieved a satisfactory pathological response. However, accuracy of pre-operative diagnoses and liver dysfunction caused by NAC were serious problems. Easy introduction of NAC for initially resectable CRLM should not be performed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

The aim of this study was to identify biomarkers for predicting the efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric cancer using microarrays of biopsy specimens before chemotherapy.. Nineteen samples were taken from 19 patients with unresectable metastatic gastric cancer who received DCS as a first-line therapy. Laser capture microdissection was performed, and total cellular RNA was extracted from each microdissected sample. Whole-gene expression was analyzed by microarray, and the difference in mRNA expression observed with the microarrays was confirmed by quantitative real-time PCR. Immunohistochemical staining was performed using clinical tissue sections obtained by endoscopic biopsy.. Eleven patients were identified as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine genes showed significant differences in relative expression ratios between tumor and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for distinguishing gene expression between 11 early responders and 8 nonresponders. Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for validation were well correlated with those 4 genes in microarrays.. The genes identified may serve as efficient biomarkers for personalized cancer-targeted therapy.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Microarray Analysis; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome

A phase II study of S-1 plus leucovorin (LV) given in a 4-week schedule (2 weeks' administration followed by 2 weeks' rest) for patients with untreated metastatic colorectal cancer (mCRC) showed that the combination was effective, but grade 3 toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2-week schedule of S-1 plus LV. Patients with mCRC received oral S-1 (40-60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated until disease progression or unacceptable toxicity. The primary endpoint was response rate. The pharmacokinetics of S-1 and LV in Chinese patients were evaluated on day 1 of the first cycle. Seventy-three patients were enrolled in Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the disease control rate was 83.1%. Median progression-free survival and median overall survival were 6.5 and 24.3 months, respectively. The incidences of grade 3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia 9.7%. There were no treatment-related deaths. The pharmacokinetics profiles of S-1 plus LV in Chinese patients were similar to those in Japanese patients. This 2-week schedule of S-1 plus LV showed good efficacy and better tolerability than the 4-week schedule. This therapy will be the base regimen for mCRC to be added by other cytotoxic or molecular-targeted drugs. The optimized treatment schedule for S-1 plus LV was 1 week on and 1 week off.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; China; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Stomatitis; Survival Analysis; Tegafur; Treatment Outcome

The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse-type adenocarcinoma involving the gastroesophageal junction or stomach.. Eligibility criteria included untreated, measurable, advanced diffuse adenocarcinoma confirmed by central pathology and performance status of 0-1. Patients were randomized (2 : 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out.. Overall, 361 patients were randomized (S-1/cisplatin, n = 239; 5-FU/cisplatin, n = 122); half (51%) were men, and median age was 56.0 years. In each group, median number of treatment cycles per patient was 4 (range, S-1/cisplatin: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two groups {median OS with S-1/cisplatin, 7.5 [95% confidence interval (CI): 6.7, 9.3]; 5-FU/cisplatin, 6.6 [95% CI: 5.7, 8.1] months; hazard ratio, 0.99 [95% CI: 0.76, 1.28]; P = 0.9312}. Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P = 0.01), but progression-free survival and time to treatment failure were not different. Safety was similar between the 2 groups; however, fewer patients treated with S-1/cisplatin than 5-FU/cisplatin had ≥1 grade 3/4 treatment-emergent adverse event or ≥1 adverse event resulting in treatment discontinuation. One treatment-related death occurred in each group. Slow accrual led to early termination.. These data suggest that S-1/cisplatin and 5-FU/cisplatin are similar in efficacy and safety in untreated patients with advanced diffuse adenocarcinoma of the gastroesophageal junction or stomach. The primary end point was not met.. NCT01285557.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophagogastric Junction; Female; Fluorouracil; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur

Our aim was to evaluate the efficacy and safety of S-1 in heavily pre-treated patients with advanced (FIGO stage IVB) or recurrent cervical cancer.. The Institutional Review Board of our hospital approved the protocol for this retrospective phase II study. Patients with measurable disease received two oral doses of S-1 (35 mg/m(2)) daily for 4 weeks of a 6-week cycle or 2 weeks of a 3-week cycle. The antitumor effect, time to progression, overall survival, and adverse events were investigated.. We retrospectively analyzed relevant data of 28 patients with advanced or recurrent cervical cancer. Twenty-two patients had prior chemotherapy (not including chemoradiotherapy) and 27 had prior radiotherapy. The median number of prior chemotherapy regimens and cycles was 2 (range 0-4) and 7 (range 0-35), respectively. Two patients (7.1%) had partial response, and 10 patients (35.7%) had stable disease. Ten patients (35.7%) discontinued the therapy because of progressive disease. The response in 5 patients could not be evaluated because of termination of treatment in the middle of the first cycle. The disease control rate was 42.8%. After a median follow-up duration of 7.5 months, the median time to progression was 4.2 months (95% CI 2.7-5.4) and the median overall survival was 9.92 months (95% CI 9.20-NA). The two patients with partial response had received less prior chemotherapy.. Oral S-1 in palliative chemotherapy is a useful and well-tolerated treatment in heavily pre-treated patients with advanced or recurrent uterine cervical cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chemoradiotherapy; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Retrospective Studies; Salvage Therapy; Survival Rate; Tegafur; Treatment Outcome; Uterine Cervical Neoplasms

Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer. This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1, oxaliplatin, and leucovorin (SOL) in the treatment of Chinese patients with metastatic colorectal cancer (mCRC).. Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin (85 mg/m(2)) on day 1, oral S-1 twice daily (80-120 mg per day) on day 1-7, and leucovorin twice daily (50 mg per day) simultaneously with S-1, every 2 weeks.. Forty patients were enrolled in our study. In total, 296 cycles of SOL were administered. The overall response rate was 50.0%. At a median follow-up of 27 months, progression-free survival and overall survival were 7.0 months (95% confidence interval [CI] 6.0-10.6 months) and 22.2 months (95% CI 15.1-29.3 months), respectively. The most common grade 3/4 non-hematological adverse events were diarrhea (n = 8, 20.0%), nausea (n = 3, 7.5%), and vomiting (n = 3, 7.5%). The most common grade 3/4 hematological toxicities were thrombocytopenia (n = 3, 7.5%), neutropenia (n = 1, 2.5%), and abnormal alanine transaminase/aspartate transaminase levels (n = 1, 2.5%). There was one treatment-related death.. The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC.. ChiCTR-TNRC-100000838.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; China; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome; Young Adult

No salvage treatment had been established for metastatic colorectal cancer (mCRC) with mutated KRAS before the emergence of the new drugs regorafenib and TAS-102. We performed a phase II study of third-line chemotherapy with combined bevacizumab and S-1 for mCRC.. Subjects were mCRC patients with mutated KRAS who showed disease aggravation even after two regimens with oxaliplatin and irinotecan. Bevacizumab was given intravenously every 2 weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle. The primary endpoint was disease control rate (DCR).. In total, 31 subjects were enrolled between August 2009 and June 2011. Three subjects in whom antitumor effects could not be evaluated were excluded. The median follow-up period was 8.6 months. The DCR was 67.9%, the response rate 0%, median progression-free survival 3.7 months, and overall survival 8.6 months. In 30 subjects evaluated for safety, there was no treatment-related death. The most common adverse events were anorexia (grade ≥3, 20%), diarrhea (grade 3, 10%), and decreased hemoglobin (grade ≥3, 17%).. The results suggest that third-line chemotherapy with combined bevacizumab and S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Female; Humans; Male; Middle Aged; Mutation; Neoplasm Metastasis; Oxonic Acid; Proto-Oncogene Proteins p21(ras); Salvage Therapy; Tegafur

Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC.. Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/kg) and irinotecan (100 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS).. A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9 %) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7 %), acne-like rash (13.9 %), and neutropenia (11.1 %). The overall RR was 33.3 % (12/36). Of these patients, five underwent conversion surgery. Median PFS and OS were 9.5 months (95 % CI 3.5-15.4 months) and 20.1 months (95 % CI 16.7-23.2 months), respectively.. IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Panitumumab; Proto-Oncogene Proteins p21(ras); Survival Rate; Tegafur

Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we examined the efficacy and safety of the combination of cetuximab and S-1 in patients with KRAS wild-type unresectable metastatic colorectal cancer who were previously treated with irinotecan, oxaliplatin, and fluoropyrimidines.. The study was designed as a phase II, non-randomized, open-label, multicenter trial. Cetuximab was initially administered at 400 mg/m(2), followed by weekly infusion at 250 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2) orally twice daily for 28 days followed by a 14-day break, resulting in a 6-week treatment course. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), disease control rate (DCR), time to treatment failure, dose intensity, safety, and BRAF mutation status.. Thirty-seven patients were eligible. The median PFS was 5.5 months, the median OS was 13.5 months, the ORR was 29.7 %, and the DCR was 73.0 %. The relative dose intensity was 86.8 % for cetuximab and 88.1 % for S-1. Grade 3-4 adverse events that occurred in >10 % of the patient population included rash, dry skin, diarrhea, paronychia, anorexia, fatigue, mucositis, and neutropenia.. Combination therapy with cetuximab and S-1 was effective and well tolerated in patients with irinotecan-, oxaliplatin-, and fluoropyrimidine-refractory metastatic colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Survival Rate; Tegafur; Treatment Failure; Treatment Outcome

Biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) enhances antitumor activity. LV is thus often added to 5-FU-based regimens for the treatment of metastatic colorectal cancer (mCRC). A combination of S-1, oxaliplatin, and LV (SOL) was shown to be feasible, effective, and safe in a previous phase I trial. We therefore conducted a randomized phase II trial to evaluate efficacy and safety of SOL compared with mFOLFOX6.. Patients with mCRC and no prior chemotherapy were randomly assigned to receive either SOL or mFOLFOX6. SOL consisted of S-1 (40-60 mg bid) plus oral LV (25 mg bid) for 1 week and oxaliplatin (85 mg/m(2)) on day 1, repeated every 2 weeks.. Among 107 patients enrolled from July 2008 through July 2009, 105 (56 in the SOL group and 49 in the mFOLFOX6 group) were eligible and evaluated. The median progression-free survival was 9.6 months in the SOL group and 6.9 months in the mFOLFOX6 group [hazard ratio (HR) 0.83, 95 % confidence interval (CI) 0.49-1.40]. The median overall survival was 29.9 and 25.9 months, respectively (HR 0.91, 95 % CI 0.55-1.49). The response rate was 55 % in both groups. Grade 3 or 4 adverse drug reactions were neutropenia (20 % with SOL vs 41 % with mFOLFOX6), sensory neuropathy (20 vs 2.0 %), anorexia (13 vs 7.8 %), fatigue (11 vs 5.9 %), and diarrhea (11 vs 3.9 %).. SOL demonstrated promising efficacy and acceptable toxicity as first-line chemotherapy for mCRC. Further studies of SOL combined with molecular target agents are warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

Protracted low-dose infusion of irinotecan has been suggested to enhance antitumor activity. A phase II study was conducted to evaluate the safety and efficacy of oral S-1 combined with 24-hour infusion of irinotecan and intravenous bevacizumab for metastatic colorectal cancer (MCRC).. The subjects were 79 patients with MCRC; 57 were chemotherapy naïve. Irinotecan (125 mg/m(2)) was administered as a 24-hour infusion on days 1 and 15, S-1 (80 mg/m(2)) was administered orally on days 1-14, and bevacizumab (5.0 mg/kg) was given on days 1 and 15. The treatment was repeated every 4 weeks.. Median follow-up was 20.0 months, and the mean number of cycles was 7. The overall response rate was 79.7% (95% CI, 69.2-88.0), 86.0% (95% CI, 74.2-93.7) for first-line and 63.6% (95% CI, 40.7-82.8) for second-line treatment. The median progression-free survival was 16.4 months (95% CI, 13.9-21.0) for first-line and 9.4 months (95% CI, 4.9-16.5) for second-line treatment. The median overall survival was not reached. Grade 3-4 toxicities were neutropenia (43%), leukopenia (20.3%), anorexia (19.0%), and diarrhea (10.1%). Toxicity was tolerable.. Combination chemotherapy with oral S-1 and biweekly 24-hour infusions of irinotecan plus bevacizumab appears to be highly active and well tolerated both as first-line and second-line chemotherapy for MCRC.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome

A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC).. Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m(2) intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m(2) oral S-1 on days 1-14 of each cycle. The treatment was repeated every 3 weeks.. Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6%), intrahepatic and extrahepatic bile ducts in 23 (60.5%), and the ampulla of Vater in 3 (7.9%) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6% (95% CI 8.5-36.7] in the per-protocol (PP) population, and 18.4% (95%CI 6.1-30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5% (95%CI 60.6-87.6) in the PP population. The median progression-free survival was 4.4 months (95%CI 1.8-6.9), and the median overall survival was 9.0 months (95%CI 4.0-13.9) with a 1-year survival rate of 44.7% (95%CI 29.0-61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1%), 9 (25.7%), 2 (5.7%), and 2 (5.7%) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4%), anorexia (2.9%), and renal toxicity (2.9%).. Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

We evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, recommended dose for phase II (P2RD), and preliminary anticancer activity of a combination eribulin and S-1 therapeutic in metastatic breast cancer patients pretreated with anthracycline and taxane.. Patients aged 20-74 years were recruited. In level 1, patients received S-1 (65 mg m(-2)) from day 1 to 14, and eribulin (1.1 mg m(-2)) on day 1 and 8 in a 21-day cycle. In level 2, eribulin was increased to 1.4 mg m(-2). In level 3, S-1 was increased to 80 mg m(-2).. Twelve patients were enrolled into three cohorts. Planned dose escalation was completed, with one case exhibiting dose-limiting toxicity (grade 3 hypokalaemia) at level 3, without reaching the MTD. The P2RD was determined to be level 2 (eribulin 1.4 mg m(-2) and S-1 65 mg m(-2)). The most common grade 3 or 4 toxicity was neutropenia (83.3%), followed by febrile neutropenia (25.0%). Five of eleven patients (41.7%) with measurable disease had a partial response. Pharmacokinetics were characterised by dose-dependent elimination and nonlinear exposure.. Dose level 3 was not tolerated owing to febrile neutropenia development. Thus, intermediate dose level 2 was recommended for further evaluation. Preliminary antitumour activity warrants further investigation in this setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Furans; Humans; Ketones; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur; Young Adult

We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN).. Patients were randomly assigned to the UFT group (300 or 400 mg day-1 for 1 year) or the S-1 group (80, 100, or 120 mg day-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety.. A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group.. Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN.. ClinicalTrials.gov NCT00336947 http://clinicaltrials.gov/show/NCT00336947.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Safety; Squamous Cell Carcinoma of Head and Neck; Tegafur; Treatment Outcome

Chemotherapeutic regimens for elderly patients with metastatic colorectal cancer (mCRC), such as bevacizumab combined with 5-fluorouracil (5-FU) and leucovorin, often exclude oxaliplatin and irinotecan owing to the risk of toxicity. However, treatment with infusional 5-fluorouracil and leucovorin requires percutaneous port-catheter placement and other precautions, causing unnecessary stress for patients as well as healthcare workers.. We conducted a phase II study to evaluate the efficacy and safety of bevacizumab plus S-1 in elderly patients with previously untreated mCRC. Bevacizumab was given intravenously every two weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle. The primary end-point was progression-free survival (PFS). The secondary end-points were time to treatment failure, response rate (RR), overall survival (OS), treatment completion status and safety.. From October 2007 through March 2010, 56 patients were enroled. The median PFS was 9.9months, the median OS was 25.0months, and the RR was 57%. The main adverse events of grade 3 or higher were hypertension (11%), diarrhoea (9%) and neutropenia (7%).. Our results suggest that combination chemotherapy with S-1 and bevacizumab can be administered safely and continuously on an outpatient basis and is therapeutically effective in elderly patients with mCRC.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Neoplasm Metastasis; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome

This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer.. Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day(-1) based on body surface area (BSA), orally, days 1-28, every 6 weeks) or SOX (S-1 80/100/120 mg day(-1) based on BSA, orally, days 1-14, plus oxaliplatin 100 mg m(-2), intravenously, day 1, every 3 weeks). The primary end point was PFS.. Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65-1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79-1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%).. Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Survival Rate; Tegafur

A combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) plus bevacizumab has been widely used for the first-line chemotherapy of metastatic colorectal cancer (mCRC). S-1 is an oral fluoropyrimidine preparation that combines tegafur, a prodrug of 5-fluorouracil, with two modulators. Several studies of combination chemotherapy with oxaliplatin plus S-1 (SOX) conducted in Asia have reported promising efficacy and safety in patients with mCRC, suggesting the potential to replace mFOLFOX6. The SOFT trial (JapicCTI-090699) was a randomized Phase III trial designed to evaluate the noninferiority of SOX plus bevacizumab to mFOLFOX6 plus bevacizumab in patients with mCRC. This review summarizes the drug concept of S-1 and the results of clinical trials of S-1 and SOX in CRC and presents an overview of the SOFT trial.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Humans; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur; Treatment Outcome

Paclitaxel and S-1 are both effective antitumor chemotherapeutic agents for advanced gastric cancer. However, the continuous administration of S-1 for 3 weeks or more can result in unacceptable toxicities, particularly hematological toxicities. Therefore, an alternative treatment schedule (1-week administration followed by 1-week rest) is warrant for testing in order to allow continuation of the therapy. We evaluate the efficacy and safety of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer.. Patients with previously untreated advanced or relapsed gastric cancer who had measurable lesion(s) were enrolled. Paclitaxel was administered intravenously at a dose of 120 mg/m(2) on day 1 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-7 followed by a drug-free interval of 1 week every 14-day cycle.. Forty-four patients (M/F = 33/11) were enrolled. A total of 277 chemotherapy cycles were administered, with a median of six cycles per patient (range 1-12), and 19 (43.2 %) patients received up to seven cycles. The assessed overall response rate was 38.6 with 38.6 % partial response in 17 patients, 45.4 % stable disease in 20 patients, and 13.6 % progressive disease in six patients. Thirty-four patients (77.3 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.2 months (95 % CI 4.08-6.39 months) and 12.2 months (95 % CI 8.81-15.60 months). The major hematological toxicities were included grade 3 leucocytopenia in two patients (4.5 %), grade 3 neutropenia in 14 patients (40.9 %), and grade 4 neutropenia in four patients (9.0 %). Two patients (4.5 %) suffered grade 1 febrile neutropenia. All grade of the non-hematological toxicities, such as nausea, vomiting, alopecia, and diarrhea, held the proportion of 54.5 % (grade 3/4, 4.5 %), 31.8, 95.4, and 18.1 % (grade 3/4, 2.2 %), respectively.. Biweekly S-1 and paclitaxel (SPA regimen) combination therapy had promising activity with acceptable adverse toxicities. SPA regimen was easily implemented, and more patients received second-line chemotherapy. It deserved to conduct a well-designed randomized phase III study to compare this regimen with S-1-based combination treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Prospective Studies; Stomach Neoplasms; Tegafur; Young Adult

This randomized phase II trial investigated the efficacy and safety of docetaxel plus bevacizumab and S-1 plus bevacizumab in the second-line treatment of non-squamous (non-Sq) non-small-cell lung cancer (NSCLC).. Patients with non-Sq NSCLC who experienced disease progression after prior platinum-based chemotherapy with or without bevacizumab were randomly assigned to receive docetaxel plus bevacizumab (DB) once every 3 weeks or S-1 orally twice daily on days 1-14 plus bevacizumab (SB) on day 1 every 3 weeks until disease progression.. Ninety patients were randomized. The median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]=3.0-6.5) in DB and 3.5 months (95% CI=2.9-5.9) in SB. The objective response rate was significantly higher in DB than in SB (22.2% vs. 2.2%; P=0.004), whereas the disease control rates of the arms were identical (62.2% vs. 62.2%; P=1.00). Patients receiving DB were more likely to have ≥grade 3 neutropenia (93.4% vs. 4.4%) and febrile neutropenia (33.3% vs. 0%) than SB. In DB, PFS and overall survival (OS) were significantly longer among bevacizumab-naïve patients than among bevacizumab-experienced patients (median PFS: 7.2 vs. 2.9 months; P=0.004; and median OS: 21.3 vs. 14.1 months; P=0.012).. DB and SB produced modest PFS benefits in the second-line treatment of patients with advanced non-Sq NSCLC. Because of the toxicity of DB and the low response rate of SB, neither regimen warrants further investigation, excluding DB in bevacizumab-naïve patients with advanced non-Sq NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Platinum; Retreatment; Taxoids; Tegafur; Treatment Outcome

The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer.. We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m(2) on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses.. All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months.. The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; ErbB Receptors; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur; Trastuzumab

We previously reported that a triplet combination of docetaxel, cisplatin, and S-1 (DCS) is active against metastatic gastric cancer with a very high response rate of 87.1 % in a phase II study. Recently, the efficacy of trastuzumab (T-mab) for the treatment of HER2-positive gastric cancer has been reported. Therefore, we investigated the feasibility and preliminary efficacy of DCS + T-mab (DCS-T) for unresectable HER2-positive metastatic gastric cancer.. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m(2)), docetaxel (50 mg/m(2)), and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks.. The study included 16 patients: median age, 60 (34-76) years; males/females, 11:5; intestinal-type/diffuse-type histology, 11:5; and HER2 3+/2+(FISH+), 13:3. The completion rate until the third cycle was 87.5 % (14/16) (95 %CI 71.3-103.7 %). Adverse events of grade 3/4 severity during the first 3 cycles were: leukopenia/neutropenia, 50.0:75.0 %; febrile neutropenia, 12.5 %; diarrhea, 12.5 %; and stomatitis, 12.5 %. All of these side effects were manageable and well controlled. There were no treatment-related deaths. The overall response rate was 93.8 % (15/16), and the response rate in patients with measurable lesions was 100 % (15/15). The median cycle to response was only 1 (1-3 cycles). Non-curative factors disappeared in 56.3 % (9/16) of patients, and conversion surgery (R0 resection) was performed in all these cases. Pathological response rates in primary and metastatic lesions were 88.9 % (8/9) and 100 % (9/9), respectively. The median PFS and OS were not reached during the median follow-up time of 18.3 months ranged from 11.0 to 34.3 months.. DCS-T was feasible in patients with unresectable HER2-positive metastatic gastric cancer. The observed response was very promising and warrants further investigation.. UMIN000005603.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Cisplatin; Docetaxel; Drug Combinations; ErbB Receptors; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Trastuzumab

Adding leucovorin to fluorouracil is known to improve response rate and overall survival in first-line chemotherapy for metastatic colorectal cancer (mCRC). The present multicenter phase II study evaluated the efficacy and safety of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA).. Patients with unresectable and untreated mCRC received S-1 (40-60 mg bid) plus leucovorin (25 mg bid) orally for 1 week, and oxaliplatin (85 mg/m(2)) and bevacizumab (5 mg/kg) intravenously on day 1, every 2 weeks. Efficacy endpoints, including the response rate (the primary endpoint) and progression-free survival, were assessed by an independent review committee.. Of the 29 eligible patients, 25 patients (86%) had a partial response [95% confidence interval (CI) 68-96%] and the remaining four patients showed stable disease with a trend toward tumor shrinkage. The median progression-free survival was 15 months (95% CI 10-26 months). The median overall survival was not reached after a median follow-up time of 34 months. The 3-year survival rate was 54%. Curative resections of metastatic lesions were performed in eight patients (28%). Common grade 3 or 4 adverse events were neutropenia (20%), hypertension (23%), anorexia (20%), fatigue (17%), diarrhea (10%), and peripheral sensory neuropathy (53%).. The SOLA therapy showed excellent efficacy and tolerable toxicities except for peripheral sensory neuropathy in patients with mCRC. Since oxaliplatin-induced neuropathy can be alleviated by modifying its administration, SOLA is a promising candidate regimen to be compared with FOLFOX plus bevacizumab in a future phase III trial.. JapicCTI-090881.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

S-1, a novel oral prodrug of 5-fluorouracil (5-FU), and irinotecan with or without bevacizumab is known to be effective in metastatic colorectal cancer (mCRC). However, it is not clear whether S-1 and irinotecan confers benefits compared to 5-FU and leucovorin plus oxaliplatin (FOLFOX) in patients with mCRC. Our aim was to compare the efficacy and safety of these regimens.. We analyzed 187 patients with previously untreated mCRC who were enrolled in four phase II studies: SIR (S-1 and irinotecan, n = 40), SIRB (S-1 and irinotecan with bevacizumab, n = 51), FOLFOX (5-FU and leucovorin plus oxaliplatin, n = 46), and STOX (stop-and-go strategy of modified FOLFOX-6 with bevacizumab, n = 50). We evaluated efficacy and safety between SIR/SIRB and FOLFOX/STOX.. Baseline characteristics were similar in the two groups composed of SIR/SIRB (n = 91) and FOLFOX/STOX (n = 96). The overall response rates were not significantly different between the two groups (65% in SIR/SIRB vs. 52% in FOLFOX/STOX, p = 0.125). The median progression-free survival was 10.9 months in SIR/SIRB versus 12.1 months in FOLFOX/STOX (p = 0.59). The median overall survival was 27.3 months in SIR/SIRB versus 26.8 months in FOLFOX/STOX (p = 0.97). Gastrointestinal adverse events were the most common toxicities in SIR/SIRB, while neutropenia and sensory neuropathy were the most common toxicities in FOLFOX/STOX.. S-1 and irinotecan with or without bevacizumab was well tolerated and showed similar response rates and survival compared to the FOLFOX regimen. This combination should be considered as an experimental first-line treatment for mCRC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur; Treatment Outcome

The mean 5-6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial demonstrated that bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev combination chemotherapy as mCRC salvage therapy.. Major eligibility criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern Cooperative Oncology Group performance status, 0-2; and progression after administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80-120 mg/body) and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The primary endpoint was disease control rate (DCR).. A total of 31 patients were enrolled. DCR was 65% [95% confidence interval (CI), 48-100%] and the response rate was 7% (95% CI, 0.7-22%). One patient showing partial response to SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall survivals were 5.3 [95% CI, 2.1-9.3] and 9.9 [95% CI, 7.4-NA] months, respectively. The most-frequent grade-3/4 adverse events were mucositis (26%) and diarrhea (11%), which were manageable by dose reduction/interruption.. SL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC.. This study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( ID UMIN000009083 ) on 11 October 2012.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Salvage Therapy; Tegafur; Treatment Outcome

S-1 plus weekly split-dose cisplatin demonstrated promising results in previous phase I and II studies for advanced gastric cancer (AGC) patients.. In this randomized phase II study, the efficacy and safety of S-1 plus weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80-120 mg according to body surface area on days 1-14, and cisplatin 20 mg/m(2) i.v. on days 1 and 8 every 3 weeks) were compared with those of S-1 plus standard-dose cisplatin (SP) as first-line chemotherapy for AGC patients. The primary endpoint was 1-year survival rate.. Patients were randomized into two groups: 18 in the SWP arm and 19 in the SP arm. This trial was terminated early because of low patient enrollment. The 1-year survival rate was 61 % [95 % confidence interval (CI), 36-86 %] and 53 % (95 % CI, 30-75 %) in the SWP and SP arms, respectively. However, the median survival time was 12.3 months (9.9-14.6 months) and 15.7 months (4.0-27.4 months), respectively (P = 0.064). Progression-free survival was significantly shorter in the SWP arm than in the SP arm (P = 0.047). Toxicity tended to be milder in the SWP arm than in the SP arm. For approximately 40 % of patients in the SWP arm, cisplatin was omitted on day 8 and treatment delayed because of prolonged myelosuppression.. No clear benefits of adding cisplatin to S-1 in the SWP arm were demonstrated in this study. At this point, split-dose cisplatin combined with S-1 cannot be recommended for use in clinical practice.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Young Adult

Neoadjuvant chemotherapy may improve outcomes in gastric cancer. Tumor responses can be evaluated with RECIST, Japanese Classification of Gastric Carcinoma (JCGC), and histological criteria. These approaches have not yet been compared.. We analyzed two phase II trials of neoadjuvant chemotherapy using S-1 plus cisplatin. JCOG0210 included patients with linitis plastica and large ulcero-invasive tumors, whereas JCOG0405 comprised those with para-aortic or bulky lymph node metastases. Radiologic evaluations were conducted using RECIST in JCOG0405 and JCGC criteria in JCOG0210, because the latter included many patients without measurable lesions. A histological responder was defined as a patient in whom one third or more of the tumor was affected. The hazard ratios (HR) for death between responders and non-responders and response rate differences between short- and long-term survivors were estimated.. In JCOG0210 (n = 49), HR was 0.54 in JCGC responders (P = 0.059) and 0.40 in histological responders (P = 0.005). The difference in response rates between short- and long-term survivors using histological criteria (34 %, P = 0.023) was greater than that using JCGC criteria (24 %, P = 0.15). In JCOG0405 (n = 51), HR was 0.67 in RECIST responders (P = 0.35) and 0.39 in histological responders (P = 0.030). In short- and long-term survivors, respectively, RECIST response rates were 62  and 67 % (P = 0.77), whereas histological response rates were 33  and 63 % (P = 0.048).. Histological criteria showed higher response assessment validity than RECIST or JCGC criteria and yielded the best surrogate endpoint for overall survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Oxonic Acid; Proportional Hazards Models; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

Based on the results of first-line chemotherapy for advanced pancreatic cancer, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration followed by 2 weeks of drug withdrawal frequently causes adverse effects. On the other hand, we experienced in clinical practice that alternate-day administration of S-1 reduced adverse effects and were tolerable for advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multicenter cooperative prospective study to compare daily with alternate-day administration of S-1 for advanced pancreatic cancer.. Patients with advanced pancreatic cancer were eligible for enrollment in this trial. S-1 was administered at a dose of 40-60 mg twice daily, calculated according to body surface area, on Monday, Wednesday, Friday, and Sunday. Each treatment cycle was 42 days. The primary end point was overall survival (OS). Secondary end points were safety, response rate (RR), progression-free survival (PFS), and time to treatment failure (TTF).. Forty-eight patients were evaluable for response. OS as the primary end point was 8.4 months (95 % CI 5.4-10.8), and the 1-year survival rate was 29.2 %. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4 %, and the disease control rate was 79.2 %. Grade 3/4 hematological and non-hematological toxicities were minor. All of these adverse reactions were tolerable and reversible.. The current data demonstrate the mitigation of adverse effects with alternate-day administration of S-1, and this appears to be a more sustainable option for advanced pancreatic cancer.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Tegafur

The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 (GS) combination chemotherapy in patients with unresectable pancreatic cancer.. Patients were randomly assigned to receive GS (oral S-1 60 mg/m(2) daily on days 1-15 every 3 weeks and gemcitabine 1,000 mg/m(2) on days 8 and 15) or gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks). The primary endpoint was progression-free survival (PFS).. One hundred and one patients were randomly assigned. PFS was significantly longer in the GS arm with an estimated hazard ratio (HR) of 0.65 (95 % CI 0.43-0.98; P = 0.039; median 5.3 vs 3.8 months). Objective response rate (ORR) was also better in the GS arm (21.6 vs 6 %, P = 0.048). Median survival was 8.6 months for GS and 8.6 months for GEM (HR 0.93; 95 % CI 0.61-1.41; P = 0.714). Grade 3-4 neutropenia (44 vs 19.6 %, P = 0.011) and thrombocytopenia (26 vs 8.7 %, P = 0.051) were more frequent in the GS arm.. GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Tegafur; Treatment Outcome

Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer.. Patients were randomly assigned to receive docetaxel plus S-1 or S-1 alone. The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The S-1 alone group received oral S-1 on days 1-28 of a 42-day cycle. The primary end point was overall survival.. Of the 639 patients enrolled, 635 were eligible for analysis. The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group (p = 0.032). The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group (p = 0.001). As for adverse events, neutropenia was more frequent in the docetaxel plus S-1 group, but remained manageable.. As first-line treatment for advanced gastric cancer, docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone. (ClinicalTrials.gov number: NCT00287768).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Young Adult

We undertook a prospective phase II study to evaluate the efficacy of S-1 plus trastuzumab combination regimen for human epidermal-growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC).. HER2-positive MBC patients received oral administration of S-1 (80 mg/m2/day, days 1 to 28, every 6 weeks) and intravenous weekly trastuzumab (2 mg/kg), according to the results of a prior Phase I trial of our group.. A total of 28 patients were enrolled and received a median of 3.5 (range 1-10) cycles of treatment. Overall response rate and clinical benefit rate were 53.6% and 75.0%, respectively. Progression-free survival was 30 weeks. With regard to grade 3 and 4 adverse effects, leucopenia, neutropenia, increase in serum alanine aminotransferase, and diarrhea were observed.. Combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this trial.

Topics: Administration, Oral; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Prospective Studies; Receptor, ErbB-2; Tegafur; Trastuzumab

Although thoracic irradiation (TRT) is a standard treatment for elderly patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treatment outcomes are poor. We previously reported a phase I trial combining S-1, an oral 5-fluorouracil derivative, and thoracic radiation, which yielded safe and effective outcomes.. In this phase II trial, 30 patients aged 76 years or older with LA-NSCLC received S-1 (80 mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary end-point was the response rate.. The median age and pre-treatment Charlson score were 79 years and 1, respectively. The mean proportions of the actual doses of S-1 and TRT delivered relative to the planned doses were 95% and 98%, respectively. Partial responses were observed in 19 patients (63%; 95% confidence interval: 45-82%), which did not attain the end-point. At a median follow-up time of 23.7 months, the median progression-free survival and median survival times were 13.0 months and 27.9 months, respectively. No difference in efficacy was observed upon stratification by tumour histology. Toxicities were generally mild, except for grade 3 or greater febrile neutropenia and pneumonitis in 7% and 10% of patients, respectively. No patient developed severe oesophagitis.. Although the primary end-point was not met, concurrent S-1 chemotherapy and radiotherapy yielded favourable survival data. Also, the combined treatment was well-tolerated in elderly patients with LA-NSCLC.

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

We report updated progression-free survival (PFS) and overall survival (OS) data from a trial that compared capecitabine plus oxaliplatin (CapeOX) versus S-1 plus oxaliplatin (SOX) for the first-line treatment of metastatic colorectal cancer.. This trial was a randomized, two-armed, non-inferiority phase 3 comparison of CapeOX (capecitabine 1000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1) versus SOX (S-1 40 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1). The primary end point was to show non-inferiority of SOX relative to CapeOX in terms of PFS. Thus, a follow-up exploratory analysis of PFS and OS was performed.. The intention to treat (ITT) population was comprised of 340 patients (SOX arm: 168 and CapeOX arm: 172). The updated median PFS was 7.1 months (95% CI 6.4-8.0) in the SOX group and 6.3 months (95% CI 4.9-6.7) in the CapeOX group (hazard ratio [HR], 0.83 [0.66-1.04], p = .10). The median OS was 19.0 months (95% CI 15.3-23.0) in the SOX group and 18.4 months (95% CI 14.1-20.7) in the CapeOX group (HR, 0.86 [0.68-1.08], p = .19). Subgroup analyses according to principal demographic factors such as sex, age, ECOG (Eastern Cooperative Oncology Group) performance status, primary tumor location, measurability, previous adjuvant therapy, number of metastatic organs, and liver metastases showed no interaction between any of these characteristics and the treatment.. Updated survival analysis shows that SOX is similar to CapeOX, confirming the initial PFS analysis. Therefore, the SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer.. NCT00677443 and May 12 2008.

Topics: Adult; Aged; Antineoplastic Agents; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome

The present phase III study was designed to investigate the noninferiority of S-1 alone and superiority of gemcitabine plus S-1 compared with gemcitabine alone with respect to overall survival.. The participants were chemotherapy-naive patients with locally advanced or metastatic pancreatic cancer. Patients were randomly assigned to receive only gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle), only S-1 (80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle), or gemcitabine plus S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle).. In the total of 834 enrolled patients, median overall survival was 8.8 months in the gemcitabine group, 9.7 months in the S-1 group, and 10.1 months in the gemcitabine plus S-1 group. The noninferiority of S-1 to gemcitabine was demonstrated (hazard ratio, 0.96; 97.5% CI, 0.78 to 1.18; P < .001 for noninferiority), whereas the superiority of gemcitabine plus S-1 was not (hazard ratio, 0.88; 97.5% CI, 0.71 to 1.08; P = .15). All treatments were generally well tolerated, although hematologic and GI toxicities were more severe in the gemcitabine plus S-1 group than in the gemcitabine group.. Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall survival with good tolerability and presents a convenient oral alternative for locally advanced and metastatic pancreatic cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Japan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Quality of Life; Survival Analysis; Taiwan; Tegafur; Treatment Outcome

To evaluate the feasibility of a cisplatin and S-1 combination regimen for the treatment for metastatic and recurrent cervical cancers, we performed this study prior to a randomized phase III trial to evaluate the clinical benefits of a cisplatin and S-1 combination regimen compared with cisplatin alone.. Cisplatin (50 mg/m(2), intravenously on day 1) and S-1 (80-120 mg/m(2), orally twice a day between days 1 and 14) were administered every 21 days for 6 cycles in patients with advanced or recurrent uterine cervical cancer.. A total of 10 patients were enrolled in this trial. A total of 46 treatment cycles (median 6; range 1-6) were administered. All grade 3 or 4 hematologic toxicities were recorded in the 6 patients: 2 patients experienced anemia, 5 experienced neutropenia, 1 experienced thrombocytopenia, and 2 experienced febrile neutropenia. All grade 3 non-hematologic toxicities were recorded in the 6 patients, and no grade 4 non-hematologic toxicities occurred; the most frequent toxicities were hyponatremia in 3 patients, diarrhea in 2 patients, and infection in 2 patients. The patients with grade 3 diarrhea had received prior radiotherapy. All the patients recovered from the toxicities after receiving appropriate supportive care, and no treatment-related deaths occurred. Five patients (50 %) achieved a partial response, and 1 patient (10 %) had a stable disease.. A cisplatin and S-1 combination regimen was feasible for patients with recurrent cervical cancer. Since patients who receive prior radiotherapy may experience severe diarrhea, these patients may require an S-1 dose reduction.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Pilot Projects; Tegafur; Treatment Outcome; Uterine Cervical Neoplasms

In Japan, CPT-11 is often used to treat unresectable gastric cancer in the second-line setting. However, evidence regarding benefit of second-line chemotherapy remains sparse, especially after failing S-1.. A phase II study to evaluate the efficacy and safety of weekly administration of CPT-11 at a dose of 100 mg/m(2) after failing a S-1-containing first-line treatment was planned with response rate as a primary end point. UGT1A1*6, *27, and *28 genotyping were performed in all cases, and those found to have either homozygous for *28, homozygous for *6, heterozygous for both *6 and *28, and heterozygous for *27 were rendered ineligible for the phase II trial.. Two patients of homozygous for *28, two patients of homozygous for *6, and one patient of heterozygous for *27 were found among 39 recruited patients. The median number of courses delivered was 3 courses. The overall response rate was 15.4 % and disease control rate was 65.4 %. The median time to treatment failure was 87.5 days and median overall survival was 268 days. Twenty-two (73 %) of 30 valuable patients experienced protocol-specified skip of treatment and 8 (30 %) of patients could continue treatment with dose reduction. ≥G3 neutropenia was found in 30 % and ≥G3 anorexia and diarrhea were found in 23 and 17 %, respectively.. Weekly CPT-11 at 100 mg/m(2) showed moderate response among gastric cancer patients who were refractory to S-1, but the disease control rate seemed meaningful. Even after selection of patients by UGT1A1 polymorphism of *6, *27, and *28, severe toxic events could not be prevented completely.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Camptothecin; Dose-Response Relationship, Drug; Drug Combinations; Female; Genotype; Glucuronosyltransferase; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.. Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m(-2) followed by oxaliplatin 85 mg m(-2) on day 1 and S-1 80 mg m(-2) per day from day 1 to 14 every 3 weeks. Polymorphisms in the UGT1A1, UGT1A6, UGT1A7 and CYP2A6 genes were analysed.. Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4-81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of UGT1A6*2 or UGT1A7*3 and an improved tumour response was noted in those without variant alleles of CYP2A6 or UGT1A1*60.. The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Camptothecin; Colorectal Neoplasms; Cytochrome P-450 CYP2A6; Drug Combinations; Female; Glucuronosyltransferase; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pharmacogenetics; Polymorphism, Genetic; Tegafur

To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer.. This study included patients who had been diagnosed with unresectable, locally advanced or metastatic adenocarcinoma arising from the pancreas, which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion. The regimen consisted of intravenous 1,000 mg/m(2) gemcitabine on day 1 and 8 combined with oral S-1 on days 1-14 every 21 days. The dosage of S-1 was based on the body surface area (BSA) as follows: 40 mg bid (total 80 mg/day) for a BSA of <1.25, 50 mg bid (total 100 mg/day) for a BSA of ≥1.25 but <1.5, and 60 mg bid (total 120 mg/day) for a BSA of ≥1.5. Treatment consisted of at least 2 courses unless rapid disease progression was noted. The primary end points were the response and disease control rates, and the secondary end points were toxicity and survival.. Thirty-seven patients were enrolled between August 2005 and December 2010. The median number of chemotherapy cycles was 4 (range 1-28 cycles). Response to treatment could be evaluated in 31 patients. None of the patients showed complete response, but 5 achieved partial response. The response rate was thus 13.5 % [95 % confidence interval (CI) 2.7-24.3 %] in the intent-to-treat population. Sixteen patients (43.2 %; 95 % CI 27-59.5 %) showed stable disease, and the overall disease control rate was 56.8 % (95 % CI 40.6-72.9 %). For all 37 patients, the median progression-free survival was 4.6 months (95 % CI 1.8-7.6 month), and the median overall survival was 9.4 month (95 % CI 5.8-12.6 month). Chemotherapy-related grade 3/4 hematological toxicities were neutropenia (36.1 %), leucopenia (22.2 %), and anemia (13.9 %). The non-hematological toxicities were generally mild.. Combination chemotherapy with gemcitabine and S-1 was effective, convenient, and safe in patients with advanced pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Survival Rate; Tegafur; Treatment Outcome

We conducted a phase I study of S-1 combined with irinotecan and oxaliplatin (TIROX) to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety, pharmacokinetics, pharmacogenetics, and preliminary efficacy in patients with metastatic colorectal cancer (MCRC) or metastatic gastric cancer (MGC).. Patients received escalating doses of S-1 (30-40 mg/m² b.i.d.) orally on days 1-14, an escalating dose of intravenous irinotecan (120-150 mg/m²) on day 1, and a fixed dose of intravenous oxaliplatin (85 mg/m²) on day 1 every 3 weeks.. Twenty-three patients (10 MCRC, 13 MGC; 13 chemonaive, 10 previously treated for metastatic disease) were treated across six dose levels. Because only one patient experienced a dose-limiting toxicity of grade 3 anorexia at the highest dose level (S-1 40 mg/m² b.i.d., irinotecan 150 mg/m², and oxaliplatin 85 mg/m²) (n = 8), the MTD was not obtained, and this level was established as the RD. With a median of 10 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (43 %), diarrhea (13 %), and nausea (13 %). In 22 efficacy-evaluable patients, the objective tumor response rate was 59.1 % (75 % for both MCRC and MGC in the first-line setting) and the disease control rate was 100 %. The exploratory pharmacokinetic/pharmacogenetic study showed that CYP2A6 variants (*4, *7, *9) are associated with a lower metabolic ratio of S-1 (exposure ratio of 5-fluorouracil to tegafur).. The new triplet TIROX regimen has shown promising antitumor activity and a favorable toxicity profile in patients with MCRC and MGC.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Camptothecin; Cohort Studies; Colorectal Neoplasms; Cytochrome P-450 CYP2A6; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Half-Life; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Survival Analysis; Tegafur

S-1 is a novel oral anticancer agent consisting of tegafur, a prodrug of 5-fluorouracil, and 2 modulators. A phase I study of sequential S-1 and cyclophosphamide(CPA)therapy was conducted to determine the dose-limiting toxicities(DLTs)and recommended doses(RDs)in patients with metastatic or recurrent breast cancer(MBC). Patients with MBC received sequential S-1 and CPA. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at escalating doses of 40, 50, 65, and 80mg/m2/day and CPA at 100 mg/body/day on days 15-28. The schedule was repeated twice at a 4-week interval. The purposes of this study were to determine the RDs, safety, and efficacy of the regimen. A total of 12 patients were registered. No patients experienced DLTs, and the RDs of S-1 and CPA were 80mg/m2/day and 100 mg/body/day, respectively. The response rate was 50. 0%. In conclusion, sequential therapy with S-1 and CPA could be safely and effectively used for the treatment of MBC, and the RDs for this regimen were determined to be 80mg/m2/day for S-1 and 100 mg/m2/day for CPA.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Recurrence; Tegafur

Combined chemotherapy with S-1 and irinotecan (IRIS) for metastatic colorectal cancer has been reported to be effective and safe. However, there are only a few studies on the effects of adding bevacizumab to IRIS. We conducted a clinical study to evaluate the efficacy and safety of IRIS plus bevacizumab as first-line therapy for metastatic colorectal cancer.. Forty metastatic colorectal cancer patients were enrolled in this phase II study. All patients received irinotecan (80 mg/m(2)) and bevacizumab (7 mg/kg) on days 1 and 15 and S-1 (40-60 mg twice daily) on days 1-21 of a 5-week repeated cycle.. The response rate was 47.4% [95% confidence interval (CI) 31.5-63.2], progression-free survival was 11.9 months (95% CI 9.4-16.8), and overall survival was 23.4 months (95% CI 19.0-inf). The only grade 3 hematological toxicity was neutropenia (16%) and the incidences of grade 3 nonhematological toxicity were low at <10%, other than diarrhea (10.9%).. In this clinical study, we revealed IRIS plus bevacizumab to be a promising first-line regimen for metastatic colorectal cancer with a low incidence of serious toxicities, in which favorable response rates and extension of survival time can be expected.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur

The aim of this study was to evaluate the efficacy and toxicity of low dose of docetaxel in combination with standard dose of S-1 for patients with advanced or recurrent gastric cancer and to investigate whether the protein expression level of dihydropyrimidine dehydrogenase is a predictive factor of toxicities or responses.. Between March 2010 and December 2011, 61 patients from the Department of Medical Oncology of Shanghai Zhong Shan Hospital, Fudan University, were enrolled in the study. Patients with advanced or recurrent gastric adenocarcinoma were treated with docetaxel of 40 mg/m(2) intravenously on day 1 and S-1 of 80 mg/m(2) orally on days 1-14 every 3 weeks as first-line chemotherapy. The chemotherapeutic effects were evaluated following every 3 cycles of chemotherapy using the Response Evaluation Criteria In Solid Tumors (RECIST). The serum of peripheral blood was obtained at the start of the study and at each evaluation point to analyze the protein expression level of DPD, which was estimated using an enzyme-linked immunosorbent assay. All the patients were followed-up until the time of progression, death, or the censor time, to calculate progression-free survival and overall survival (OS) time.. In total, 61 patients [median age 60 years (range 28-76 years)] received a total of 318 treatment cycles [median 5 (range 2-9)], and 94 cycles of single S-1 maintenance treatment. One complete response (CR) and 25 partial responses (PR) were observed, with an overall response rate of 42.6%. A total of 29 patients (47.5%) had stable disease (SD) and 6 patients (9.8%) had progressive disease (PD). The disease control rate (DCR, CR + PR + SD) was 90.2%. Median overall survival was 13.0 months [95% confidence interval (CI) 10.76-15.24 months], and median PFS was 6.0 months (95% CI 4.61-7.39 months). Progression-free survival was far longer in peritoneal metastatic patients than that in patients with other metastases (7.3 ± 2. 6 vs. 5.4 ± 2.8 months; P < 0.05); however, this was not the case for OS. Grade 3-4 neutropenia was well controlled and grade 4 non-hematologic toxicities did not occur. Baseline expression level of DPD was not associated with efficacy. Lower expression level of DPD was correlated with high grade of toxicities (P < 0.05).. This combination of standard dose of S-1 and low dose of docetaxel is effective and well tolerated in patients with advanced or recurrent gastric cancer. Peritoneal metastasis is treated more effectively by this regimen than other forms of metastases. Baseline DPD expression level in the serum is associated with toxicity, but not tumor response.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dihydrouracil Dehydrogenase (NADP); Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits VEGFR-2, FGF and PDGF receptors. We conducted a phase I study to evaluate the safety and pharmacokinetic of TSU-68 when used with S-1 and oxaliplatin (SOX) in metastatic colorectal cancer (mCRC) patients. Patients with mCRC were treated with TSU-68 200 mg (Level 1) or 400 mg (Level 2) b.i.d. daily, S-1 35 mg/m(2) b.i.d. on Days 1-14 and oxaliplatin 130 mg/m(2) i.v. on Day 1 repeatedly every 3 weeks. Of eleven patients enrolled, two patients were excluded from dose limiting toxicity (DLT) assessment. Six patients at Level 1 experienced no DLT. Of three patients at Level 2, two patients experienced DLTs (one patient: grade 3 hiccup and palmar-plantar erythrodysaesthesia syndrome, another one: grade 2 neutropenia which prevented the initiation of next cycle within 14 days). The maximal tolerated dose (MTD) and recommended dose (RD) of TSU-68 was 200 mg b.i.d. C(max) and AUC(0-t) of TSU-68 at Level 2 were higher than those at Level 1, but doubling the dose of TSU-68 increased C(max) and AUC(0-t) less than two-fold. There was no appreciable difference in the PK of S-1 components (FT, CDHP and Oxo), 5-FU and oxaliplatin-derived platinum between Levels 1 and 2. A significant decrease in PDGF after TSU-68 treatment was identified and it might serve as pharmacodynamic marker of TSU-68. Administration of TSU-68 in combination with SOX is generally well tolerated. The MTD and RD of TSU-68 in this study was 200 mg b.i.d. daily.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Female; Fibroblast Growth Factors; Humans; Indoles; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxindoles; Oxonic Acid; Platelet-Derived Growth Factor; Propionates; Protein Kinase Inhibitors; Pyrroles; Tegafur; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2

Fluorouracil (5-FU) plus irinotecan combined with bevacizumab has significant activity in metastatic colorectal cancer (mCRC), but S-1 has become a substitute for continuous infusion of 5-FU and has a very low incidence of hand-foot syndrome. With the S-1 plus irinotecan regimen (SIR), the response rate was 62.5%, and the progression-free survival was 8.0 months. We report here on an update of efficacy and safety of the SIR plus bevacizumab (SIRB) regimen as first line treatment for mCRC patients. Fifty-one eligible patients with histologically confirmed advanced or recurrent colorectal cancer received this treatment. S-1 was administered orally on days 1-14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg, 50 mg, or 60 mg. Irinotecan (150 mg/m(2)) plus bevacizumab (7.5 mg/kg) were administered by intravenous infusion on day 1. Safety analysis identified a grade 3/4 neutropenia rate of 26%. Other grade 3/4 toxicities were diarrhea (8%), nausea (6%), vomiting (2%), and hypertension (8%). The response rate was 67% and the median progression-free survival time was 373 days. The SIRB regimen appears to be highly active and well tolerated as first-line treatment for mCRC.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur; Treatment Outcome

The current study aimed to assess the long-term efficacy of combination therapy with oral S-1, a fluoropyrimidine prodrug, plus irinotecan in previously untreated patients with metastatic colorectal cancer.. Between April 2004 and February 2005, 41 patients with previously untreated advanced or recurrent colorectal cancer were enrolled in the study. Chemotherapy consisted of oral administration in S-1 at 40 mg/m(2) twice daily on days 1 to 14 and intravenous infusion of irinotecan at 150 mg/m(2) on day 1 in a 21-day cycle.. The median patient follow-up was 78.0 months. The median survival time was 23.7 months, and the 2-year survival rate was 50%. The median time to tumor progression was 8.3 months.. The results of this long-term update confirmed that first-line combination therapy with oral S-1 plus irinotecan was effective in patients with metastatic colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Prospective Studies; Tegafur; Young Adult

Triplet combination chemotherapy has the potential to improve the prognosis of patients with unresectable gastric cancer. We conducted a phase I trial of triplet combination chemotherapy consisting of paclitaxel, cisplatin, and S-1 (PCS) for unresectable gastric cancer.. Patients with metastatic or incurable disease were enrolled. S-1 was administered on days 1-14. Paclitaxel and cisplatin were infused on days 1 and 15. The starting doses of paclitaxel and cisplatin were 100 and 20 mg/m(2), respectively. Dose levels of paclitaxel and cisplatin were escalated as follows: 120 and 20 mg/m(2), respectively (level 2); 120 and 30 mg/m(2), respectively (level 3). End-points: Dose-limiting toxicities included grade 3 nausea, vomiting, and general fatigue, and grade 4 febrile neutropenia. The maximum tolerated dose and recommended dose were established at level 3 and level 2, respectively.. Although further clinical trials are recommended to more thoroughly evaluate safety and efficacy, PCS appears to be an excellent candidate for a standard treatment strategy for unresectable gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

The present study was conducted to evaluate the efficacy and safety of a combination regimen of S-1, paclitaxel plus cisplatin in patients with advanced gastric cancer.. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 80 mg/m² plus cisplatin 30 mg/m² on days 1, 8 and S-1 35 mg/m² orally twice daily on days 1-14 based on a 3-week cycle.. Forty-four patients were enrolled in the current study, among whom 38 were assessable for efficacy and all assessable for toxicity. Two complete response and 24 partial responses were confirmed, giving an overall response rate of 59.1%. At a median follow-up of 11.4 months, the median time to progression and median overall survival was 9.4 (95% CI 6.8-12.1) months and 11.2 (95% CI 7.6-14.8) months, respectively. Grade 3/4 neutropenia occurred in 45 events (20.9%) and febrile neutropenia was observed in five events (2.3%). The common non-hematologic toxicity was nausea (grade 1/2, 27.2%) and diarrhea (grade 1/2, 9.0%).. The combination of S-1, paclitaxel and cisplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Prospective Studies; Stomach Neoplasms; Survival; Tegafur; Treatment Outcome

we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC).. treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks.. forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%.. TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Taxoids; Tegafur; Young Adult

To evaluate the efficacy, safety and pharmacokinetic profiles of S-1, which composed of tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4-dihydroxypyridine and potassium oxonate (Oxo), in Taiwanese advanced gastric cancer (AGC) patients.. Patients with chemo-naïve, histologically confirmed AGC were eligible. S-1 was given orally at dose of 40, 50 or 60 mg, twice daily for patients with body surface <1.25, 1.25-1.5 and >1.5 m(2), respectively, on day 1-28 every 42 days/cycle.. Thirty-four patients were included. On intent-to-treat analysis, the overall response rate, median progression-free and overall survival were 35.3% [95% confidence interval (CI): 19.2-51.3%], 2.9 (95% CI: 2.4-5.8) months and 9.8 (95% CI: 6.1-NA) months, respectively. The most common grade 3-4 toxicities were anemia 23.5% and neutropenia 11.8%. There were two treatment-related mortality, which occurred in patients with suboptimal renal function underestimated by serum creatinine level at study entry. Single-dose pharmacokinetic study showed trend toward lower AUC(5-FU), and higher AUC(FT) and AUC(Oxo) comparing to most Western reports.. The efficacy, toxicity and pharmacokinetic profiles of S-1 in current study are compatible with those from other Asian populations. Accurate renal function assessment and more closely monitoring is mandatory for S-1 therapy in patients with low body mass. Literature review suggests that, besides AUC(5-FU), AUC(Oxo) may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Asian People; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taiwan; Tegafur

To evaluate the efficacy and safety of S-1 in combination with oxaliplatin in a biweekly schedule as first-line treatment in metastatic colorectal cancer and the association between genetic polymorphisms and treatment outcomes.. Eligibility included age 18-75 years, at least one measurable lesion, no prior chemotherapy except adjuvant chemotherapy, and Eastern Cooperative Oncology Group Performance Status (PS) 0-2. S-1 40 mg/m(2) b.i.d. on days 1-7 with 85 mg/m(2) of oxaliplatin on day 1 was repeated every 2 weeks. Genomic DNA from whole blood was analyzed for 15 single-nucleotide polymorphisms (SNPs) among 8 genes.. Fifty-two patients (median age 63 years, range 37-74) were enrolled: 37 men and 15 women; 44 with a PS of 0 and 8 with a PS of 1; and 41 with initially metastatic cancer and 11 with relapsed disease. Among 51 evaluable patients, objective response rate was 47.1% [95% confidence interval (CI) 32.9-61.2]. Median follow-up duration was 17.1 months (range 3.9-28.2 months). Median progression-free survival (PFS) was 6.4 months (95% CI 4.8-8.1), and median overall survival had not been reached yet. Reported grade 3 toxicities were neutropenia (7.7%), thrombocytopenia (5.8%), sensory neuropathy (7.7%) and diarrhea (1.9%). There was no grade 4 toxicity or neutropenic fever. Patients with A/G or G/G genotype in GSTP1 Ile105Val SNP had longer PFS than patients with A/A (median 8.3 vs. 6.1 months, P = 0.04).. Biweekly S-1 with oxaliplatin is effective and has improved tolerability and convenience compared to other fluoropyrimidine with oxaliplatin combinations. GSTP1 Ile105Val SNP is associated with treatment outcomes.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxonic Acid; Polymorphism, Single Nucleotide; Prospective Studies; Pyridines; Tegafur

We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer.. Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0-2 and no prior chemotherapy history were eligible for inclusion (n = 45). Patients received a total of 215 treatment courses (median, 4; range, 2-12) of S-1 oral administration twice daily for 1 week followed by a drug-free interval of 1 week. Docetaxel (40 mg/m(2)) was administered intravenously on days 1 and 15.. We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3 months, the median time to progression was 6.9 months, and the median duration of response in 26 patients was 8.0 months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths.. S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

We aimed to evaluate the efficacy and safety of gemcitabine/S-1 combination chemotherapy for the treatment of patients with advanced biliary tract cancer.. Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were eligible for inclusion. The primary endpoint was overall survival. Gemcitabine was administered intravenously at a dose of 1,000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 was administered daily at a dose of 60 mg/m(2) on days 1-14. This schedule was repeated every 3 weeks until disease progression or patient refusal.. Twenty-five patients were enrolled between October 2007 and January 2009. Eleven patients (44%) had extrahepatic bile duct cancer, 5 (20%) had intrahepatic bile duct cancer, 8 had gallbladder cancer (32%), and 1 (4%) had ampulla of Vater cancer. The median overall survival time was 12.7 months (95% CI, 8.4-23.5 months), and the 1-year survival rate was 52.0% (95% CI, 31.2-69.2%). Of the 23 patients with evaluable target regions, seven patients experienced a partial response, and an overall response rate was 30.4%. The following grade 3-4 hematological toxicities occurred: neutropenia (56%), leukopenia (24%), anemia (8%) and thrombocytopenia (4%). In spite of the high incidence of grade 3-4 neutropenia, no patients developed febrile neutropenia in the present study. The major grade 3-4 non-hematological toxicities were fatigue (8%), anorexia (8%) and diarrhea (4%).. Gemcitabine/S-1 combination chemotherapy offered a promising survival benefit with acceptable toxicity in patients with advanced biliary tract cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

The aim of this study was to investigate the efficacy and safety of S-1/irinotecan/oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and the association between treatment outcome and uridine diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms.. Patients with previously untreated MGC received S-1 40 mg/m(2) b.i.d. on days 1-14 and irinotecan 150 mg/m(2) plus oxaliplatin 85 mg/m(2) on day 1 every 3 weeks.. Forty-four patients were enrolled. In intent-to-treat analysis, the objective response rate was 75%, including the complete response (CR) rate of 14%. The median time to progression and overall survival was 10.2 and 17.6 months, respectively. Ten (26%) of the 39 patients with primary gastric tumor showed biopsy-confirmed gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. The most common grade 3 nonhematologic toxic effects were abdominal pain (18%), anorexia (16%), and diarrhea (14%). UGT1A polymorphisms were associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, and UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), and grade 3 abdominal pain (UGT1A1*6).. The TIROX regimen induced marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. UGT1A genotype may be predictive of TIROX toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Glucuronosyltransferase; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Tegafur; Treatment Outcome

This single-arm, phase II clinical study evaluated the efficacy and safety of sequential treatment with S-1 followed by cisplatin in patients with advanced or recurrent gastric cancer.. Fifty patients with histologically confirmed advanced or recurrent gastric cancer and an Eastern Cooperative Oncology Group performance status of 0-2 who had measurable and/or assessable lesions and gave written informed consent were enrolled. S-1 (40 mg/m(2), bid) was administered on days 1-21, and cisplatin (70 mg/m(2)) was given as an intravenous infusion on day 22 of a 35-day cycle. Treatment was continued until disease progression or intolerable adverse events. Cisplatin was administered for 6 cycles. Adverse events were assessed according to Common Terminology Criteria of Adverse Events version 3.0, and efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.0 for patients with measurable lesions and by the criteria of the Japanese Research Society for Gastric Cancer for all patients.. Efficacy could be evaluated in 49 of the 50 enrolled patients. The median age was 62 years. Lesions were measurable in 38 patients and assessable in 11. The response rate was 44.7% in patients with measurable lesions and 40.8% overall. The progression-free survival and overall survival were, respectively, 233 days (7.8 months) and 574 days (19.0 months) in patients with measurable lesions and 192 days (6.4 months) and 402 days (13.4 months) overall. Serious adverse events (grade 3 or higher) included neutropenia (24.5%), anemia (20.4%), and anorexia (20.4%) and were safely managed.. The safety and effectiveness of sequential treatment with S-1 followed by cisplatin every 35 days is equivalent to that reported for conventional chemotherapeutic regimens in patients with advanced or recurrent gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

To investigate the combination of S-1 and irinotecan (CPT-11) as an alternative to infusional 5-fluorouracil/leucovorin plus CPT-11, we performed a phase I trial to determine the maximum tolerated dose, recommended dose (RD), and dose-limiting toxicities (DLTs) in patients with metastatic or recurrent colorectal cancer.. S-1 and CPT-11 doses were escalated using a standard 3 + 3 design. S-1 was administered orally at 70 mg/m(2) (levels 1-3) or 80 mg/m(2) (levels 4 and 5) for 14 consecutive days followed by 1-week rest. CPT-11 was administered intravenously on day 1, at 175 mg/m(2) (level 1), 200 mg/m(2) (level 2), 225 mg/m(2) (levels 3 and 4), or 250 mg/m(2) (level 5). Treatment was repeated every 3 weeks, unless disease progression or severe toxicities were observed.. Twenty-three patients were treated. One patient at each of levels 2 and 4 developed a DLT, grade 3 ileus, and grade 3 diarrhea, respectively. At both levels, an additional three patients did not experience DLTs. At level 5, two of five patients experienced DLTs, including grade 3 enteritis and grade 4 neutropenia for more than 5 days. The RD was determined at level 4 (80 mg/m(2) S-1 and 225 mg/m(2) CPT-11). An objective response was observed in 7 of 17 patients with measurable disease: 2 of 5 at level 2; 3 of 4 at level 4; and 2 of 4 at level 5.. The RDs of CPT-11 and S-1 were determined as 225 and 80 mg/m(2), respectively, and further phase II trials are warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Treatment Outcome

A combination of fluorouracil and leucovorin (5-FU/LV) with oxaliplatin (FOLFOX) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. A strategy to stop FOLFOX, deliver 5-FU/LV as a maintenance therapy and reintroduce FOLFOX was found to be equivalent in terms of efficacy while neurotoxicity was substantially reduced. The aim of this study was to evaluate feasibility of a stop-and-go strategy with S-1, an oral fluoropyrimidine derivative, as a maintenance therapy administered between modified FOLFOX6 (mFOLFOX6) as a first-line treatment of mCRC.. Thirty patients with untreated mCRC were treated with six cycles of mFOLFOX6 followed by maintenance therapy with oral S-1. Reintroduction of mFOLFOX6 was scheduled after four cycles of S-1 or upon tumor progression. The primary endpoint was duration of disease control (DDC).. Twenty-one of the 30 patients who achieved responses or stabilizations received S-1 maintenance therapy. mFOLFOX6 was reintroduced in 15 patients. Median DDC and progression-free survival were 9.3 and 7.9 months, respectively. The response rates and disease control rates were 40.0 and 86.6% for the initial mFOLFOX6, 23.8 and 57.1% for S-1 maintenance therapy and 20.0 and 73.3% for mFOLFOX6 reintroduction, respectively. Twenty-eight patients (93.3%) had peripheral neuropathy, but grade 3 neurotoxicity was observed in only 1 patient (3.3%).. The planned oxaliplatin stop-and-go strategy with oral S-1 maintenance therapy was feasible as a first-line treatment for Japanese mCRC patients. Further prospective randomized control study is warranted.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

S-1 is a rationally designed oral agent that combines the 5-fluorouracil prodrug tegafur with gimeracil and oteracil, which inhibit 5-fluorouracil degradation by dihydropyrimidine dehydronase and phosphorylation within the gastrointestinal tract, respectively, to increase antineoplastic activity while reducing gastrointestinal toxicity. We investigated the activity and toxicity of S-1 in combination with cisplatin in patients with unresectable non-small cell lung cancer (NSCLC).. Cisplatin, 75 mg/m, was administered intravenously on day 1, with S-1, 25 mg/m PO two times a day, days 1 to 14, every 21 days for a maximum of six cycles. Primary end point was overall response.. A total of 58 patients received at least one cycle of protocol-specified therapy. The best overall response rate was 23.2% (95% confidence interval: 13.0-36.4), and the disease control rate was 67.9%. The median progression-free survival was 4.0 months (95% confidence interval: 3.3-5.5). There did not appear to be any relationship between response to therapy and tumor histology. The most frequently reported adverse events of G3 or more (≥10%) were neutropenia (28%), hyponatremia (19%), diarrhea (17%), hypokalemia (12%), fatigue (10%), dehydration (10%), and deep vein thrombosis (10%).. Although the S-1 + cisplatin regimen used in this study appeared to have a similar level of antitumor activity and toxicity to that of established cisplatin-based doublets in NSCLC, the protocol-specified criteria of sufficient efficacy to warrant further study with an objective response rate ≥30% was not achieved. Therefore, while S-1 appears to be a promising agent in NSCLC, further evaluation should be conducted to determine the optimal S-1-based regimen to take forward for additional study.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer.. Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks.. A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one dose of gemcitabine and S-1 combination therapy. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥Grade 3.. Gemcitabine and S-1 combination therapy produced a high response rate with good survival in patients with metastatic pancreatic cancer. A randomized Phase III study to confirm the efficacy of gemcitabine and S-1 combination therapy is ongoing.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Thrombocytopenia; Treatment Outcome

As there are no reports of S-1 in combination with trastuzumab in clinical settings, we evaluated the safety and efficacy of S-1 in combination with trastuzumab for human epidermal-growth factor receptor (HER2)-positive metastatic breast cancer (MBC) and determined the recommended dose (RD).. Patients with HER2-positive MBC received trastuzumab (a fixed initial dose of 4 mg/kg/day, then 2 mg/kg every week) plus S-1 (4 weeks followed by a 2-week rest) every 42 days. The dosage of S-1 was set of three levels (1: 80 mg/m², 2: 65 mg/m², 3: 50 mg/m²). The purposes of this study were the determination of the RD and safety. Dose-limiting toxicity (DLT) data were continually monitored to assess S-1 dose decreases.. Twelve patients were treated at level 1. Because no patients experienced DLT, the RD of S-1 plus trastuzumab therapy was 80 mg/m² S-1 and 4 mg/kg followed by 2 mg/kg trastuzumab. The overall response rate and disease control rate were 33.3% and 83.3%, respectively.. S-1 plus trastuzumab could be safely and effectively used for the treatment of HER2-positive MBC. The RD for a phase II study of this regimen was determined to be 80 mg/m² S-1 and 2 mg/kg trastuzumab every week (loading dose, 4 mg/kg).

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Female; Genes, erbB-2; Humans; Neoplasm Metastasis; Oxonic Acid; Tegafur; Trastuzumab

This is a randomized phase II trial to evaluate non-inferiority of progression-free surviva(l PFS) by comparing S-1 and S-1/PSK for advanced or recurrent gastric cancer. Sample size was calculated to be 120. However, the trial was terminated because of slow accrual. This exploratory analysis was done by collecting the minimum data.. Only 8 patients were enrolled. Four patients were randomly assigned to S-1 and the others to S-1/PSK. Performance status was 0 in all 8 patients. Median age was 64. Median overall survival was 13.7 months in all 8 patients, 8 . 9 months in S-1 group, and 13 . 7 months in S-1/PSK group.. When considering PS 0 in 8 patients enrolled, an overall survival was comparable to that observed in S-1 group of other phase III trials. Standard chemotherapy for advanced gastric cancer was changed to S-1/CDDP by SPIRITS phase III trial which was presented just after this trial was initiated, which would be a major cause of slow accrual. When conducting phase III trial, we should carefully determine design and standard arm by considering on-going phase III trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Proteoglycans; Recurrence; Stomach Neoplasms; Tegafur

S-1, a novel oral fluoropyrimidine, is well tolerated in patients with metastatic colorectal cancer (mCRC). The response rate of S-1 for colorectal cancer is high, ranging from 35% to 40%. This study aimed to evaluate the safety and efficacy of S-1 combined with oral leucovorin (LV) to enhance antitumor activity in chemotherapy-naive patients with mCRC.. S-1 was given orally twice daily for two consecutive weeks at a daily dose of 80-120 mg, followed by a 2-week rest period, within a 4-week cycle. LV was given orally twice a day at a daily dose of 50 mg, simultaneously with S-1.. Of the 56 patients with previously untreated mCRC, 32 (57%) had partial responses. The median follow-up period was 27.2 months. The median time to progression was 6.7 months (95% confidence interval 5.4-7.9). The median survival time was 24.3 months. There was no treatment-related death or grade 4 toxicity. The most common grade 3 toxic effects were diarrhea (32%), anorexia (21%), stomatitis (20%), and neutropenia (14%).. S-1 combined with LV therapy demonstrated promising efficacy and acceptable safety in chemotherapy-naive patients with mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colorectal Neoplasms; Disease Progression; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome

We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer.. Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0-2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m(2)) and docetaxel (60 mg/m(2)) on day 8 every 3 weeks.. Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44-77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0-1,138.1] and 226 days (95% CI, 182.5-379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed.. DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Granulocyte Colony-Stimulating Factor; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome

The purpose of the present phase II study was to evaluate both the efficacy and toxicity of the combination of S-1 and docetaxel in previously treated patients with locally advanced or metastatic non-small cell lung cancer.. Thirty-eight previously treated patients with non-small cell lung cancer were treated with S-1 (80 mg/m(2), days 1-14, oral) and docetaxel (40 mg/m(2), day 1, intravenous) every 3 weeks.. No complete response was observed, and seven patients had a partial response, yielding an overall response rate of 18.4% (95% CI, 7.7-34.3%). The median overall survival time and 1-year overall survival rate were 16.1 months and 60%, respectively. The median progression-free survival time was 4.4 months. Myelosuppression was the main toxicity with grade 3 or 4 neutropenia and leukopenia in 50 and 21%, respectively. There was no irreversible toxicity in this study.. The combination of S-1 and docetaxel is well tolerable and has substantial activity for patients with locally advanced or metastatic non-small cell lung cancer. A phase III trial comparing docetaxel with or without S-1 would warrant further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Survival Rate; Taxoids; Tegafur; Treatment Outcome

This study was conducted to identify a recommended dose for S-1, used in combination with 40-Gy radiation.. Thirty patients, 15 each with stage III and IVA oral carcinoma, were enrolled. All patients received a total dose of 40-Gy. For the S-1 treatment, patients were given either the standard Japanese dose, calculated according to body surface area, or a reduced dose. Groups consisting of at least three patients were given S-1 according to one of 8 regimens.. Hematologic toxicity was mild and reversible. The most common nonhematologic toxicity was mucositis. At level 8 that was the standard S-1 dose for 5 days per week for 4 weeks, dose-limiting toxicity was observed when 2 patients had grade 4 mucositis. This level was thus deemed the maximum tolerated dose for the regimen.. The recommended dose of S-1 with concurrent radiotherapy was the reduced dose of S-1 given for 5 days per week, for 4 consecutive weeks. Preoperative S-1 and concurrent radiotherapy was well tolerate and feasible and warrants a phase II study.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Dose-Response Relationship, Radiation; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Oxonic Acid; Preoperative Period; Tegafur; Treatment Outcome

This randomized controlled trial will compare oral 5-fluorouracil derivatives, TS-1, with intravenous standard chemotherapy such as taxanes in women with metastatic or recurrent breast cancer. Patients with hormone-resistant breast cancer are assigned to either TS-1 (40-60 mg twice daily for 28 consecutive days, followed by a 14-day rest period) or standard chemotherapy (docetaxel 60-75 mg/m(2) at 3- or 4-week intervals, paclitaxel 175 mg/m(2) at 3- or 4-week intervals or paclitaxel 80-100 mg/m(2) weekly, followed by a 1-week rest period). Treatment will be repeated until tumor progression or > or =4 courses for TS-1 and > or =6 courses for taxanes. The primary endpoint is overall survival. Secondary endpoints are progression-free survival, time to treatment failure, adverse events, health-related quality of life and cost-effectiveness. A threshold hazard ratio of 1.333 will be used to determine whether overall survival in the TS-1 group is equivalent (not inferior) to that in the taxane group. The target number of registered patients is 600.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Cost-Benefit Analysis; Disease Progression; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Quality of Life; Survival Rate; Taxoids; Tegafur

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Humans; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Tegafur

A multicenter phase II study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus S-1 in patients with advanced gastric cancer.. Patients with previously untreated metastatic or recurrent gastric cancer received intravenous paclitaxel 50 mg/m(2) on days 1, 8, and 15, plus oral S-1 40 mg/m(2) b.i.d. on days 1 to 14 followed by 2 weeks off, in a 28-day cycle.. A total of 54 patients were registered. All of them had measurable disease and were determined to be eligible for the present study. Two complete responses and 23 partial responses were confirmed, giving an overall response rate of 46.3%. At a final follow up of 3 years, the median progression-free survival and median overall survival were 6.0 and 14.3 months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in 1 patient (total, 27.8%). The most serious nonhematological toxicity was diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatment-related deaths.. A combination of weekly paclitaxel plus S-1 was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation with comparative trials is needed for confirmation.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Confidence Intervals; Disease Progression; Drug Combinations; Female; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

Three-drug combination of fluoropyrimidine, irinotecan and oxaliplatin has shown survival benefits in patients with metastatic colorectal cancer (mCRC). Recently we performed a phase II study of a new 3-drug regimen, TIROX (S-1 plus irinotecan and oxaliplatin) to evaluate efficacy and safety in refractory mCRC patients. Patients with refractory to all of 3 drugs, age > or = 18 years, PS 0-2, > or = 1 measurable lesion(s) and adequate organ functions were eligible. S-1 was given 40 mg/m(2) twice a day on D1-14, oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) on D1 every 3 weeks. The primary endpoint was overall response rate (ORR). Between Mar 2007 and Nov 2007, 19 patients (of 18 planned) were enrolled; median age 50 years; M/F 12/7; PS 0/1/2 5/13/1; colon/rectum 11/8. By intent-to-treat analysis, ORR was 21.1% (95% CI, 8.7-43.7) and disease control rate was 52.6% (95% CI 31.5-72.8) with four PRs and six SDs. Median duration of disease control was 4.3 months (95% CI 1.7-6.9). Median PFS was 2.6 months (95% CI 2.2-2.9) and median OS was 9.8 months (95% CI 5.3-14.4) after median F/U of 15.4 months. G3/4 toxicities per pt included neutropenia (five, 26.3%), febrile neutropenia (two, 10.5%), thrombocytopenia (one, 5.3%), diarrhea (two, 10.5%) and fatigue (two, 10.5%). TIROX seemed to be feasible and efficacious for refractory mCRC patients, and could be an alternative for patients with good PS but no further treatment options.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur; Treatment Outcome

We performed a phase II study of combination chemotherapy with S-1 plus gemcitabine for treating chemo-naïve patients with unresectable pancreatic cancer to evaluate the efficacy and toxicity.. Patients with histologically confirmed unresectable pancreatic cancer were eligible. The treatment consisted of S-1 (40 mg/m(2) p.o. b.i.d. from D1 to 14) and gemcitabine (1,250 mg/m(2) on D1 and 8), repeated every 3 weeks.. Thirty-two patients were enrolled between March 2005 and December 2007. No complete response was observed and a partial response was observed in 14 patients (44.0%), stable disease in eight patients (25.0%), and progressive disease in eight patients (25.0%). The median time to progression was 4.92 months (95% CI: 4.16-5.67 months), and the median overall survival was 7.89 months (95% CI: 5.96-9.82 months). The survival duration was significantly longer for the patients with a good performance status compared with that of the patients with a poor performance status. The major toxicities were grade 3-4 neutropenia (9, 28.1%), grade 3/4 thrombocytopenia (5, 15.6%), and grade 3 diarrhea (5, 15.6%).. The combination chemotherapy of S-1 and gemcitabine showed promising antitumor activity and manageable toxicities, and especially for the good performance status patients with unresectable pancreatic cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Survival Analysis; Tegafur

To evaluate the efficacy and safety of the combination of oxaliplatin and S-1 (OS) in treating metastatic colorectal cancer.. Eligible patients were those with measurable lesions, no previous history of chemotherapy (except adjuvant chemotherapy), an age of 18-70 years, and an Eastern Cooperative Oncology Group performance status of zero to two. Oxaliplatin 130 mg/m(2) was administered i.v. on day 1, and S-1 40 mg/m(2) b.i.d. was administered orally on days 1-14, every 3 weeks.. Forty-eight patients (median age, 56 years) were enrolled: 23 had colon cancer, seven rectosigmoid colon cancer; and 18 rectal cancer. Of the 48 patients, 31 were diagnosed with metastatic cancer and 17 had relapsed cancer after surgery, with adjuvant chemotherapy or chemoradiotherapy. In total, 413 cycles were administered (median 6 per patient; range 2-24). Toxicity was evaluated in 48 patient and response in 46. Major toxic effects were grade 3/4 thrombocytopenia (13%) and neutropenia (10%). The overall response rate was 54% [95% confidence interval (CI) 40% to 68%]. The median time to progression and median survival time were 8.5 (95% CI 6.2-10.9) months and 27.2 (95% CI 20.3-34.0) months, respectively.. These data indicate that the OS regimen is effective and well tolerated in patients with advanced colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur; Time Factors; Treatment Outcome; Young Adult

The combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been reported to be active against metastatic gastric cancer (MGC) and great synergy has been shown in vivo and in vitro when 5-FU precedes CDDP. The sequential combination of S-1 (tegafur, oxonic acid, 5-chloro-2,4-dihydroxypyridine) followed by CDDP for MGC was investigated. A phase I trial applying increasing doses of oral administration of S-1 (65-80 mg/m(2)) for 21 days and increasing doses of CDDP (60-80 mg/m(2)) on day 22 every 35 days was conducted in order to determine the maximum tolerated dose (MTD) and recommended phase II dose. Patients with metastatic or recurrent gastric cancer, no prior chemotherapy, measurable disease, ECOG performance status less than 3 and adequate organ functions were eligible for the study. Three patients were treated at each dose level with escalation based on toxicity. Fifteen patients were included and evaluated for dose-limiting toxicity (DLT) and MTD. DLT included NCICTC grade 3 anorexia and fatigue in patients treated at S-1 80 mg/m(2) and CDDP 80 mg/m(2) (dose level 5). The other toxicities, grade 3 or higher, included neutropenia (grade 3) and nausea/vomiting (grade 3). Non-hematological toxicities were grade 1/2 and included diarrhea, nausea and stomatitis. There was no treatment-related mortality. Therefore, the recommended dose was a combination of S-1 at 80 mg/m(2) and CDDP at 70 mg/m(2). This sequential administration of S-1 and CDDP every 35 days is tolerable and warrants a phase II trial. A multicenter phase II study is currently under way.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur

S-1 showed clinical activity in colorectal cancer, and the preclinical data of S-1 with oxaliplatin showed synergistic activity in an animal model. This phase I study was conducted to determine the maximum tolerated dose of S-1 with oxaliplatin and to define its recommended dose for the subsequent phase II study.. Patients with untreated colorectal adenocarcinoma were eligible in this study if they had measurable lesions. S-1 was administered on days 1-14, with doses starting from 60 mg/m2 per day and escalating by 10 mg/m2 at each dose level. Oxaliplatin was given at the fixed dose of 130 mg/m2, through 2-h i.v. infusion on day 1. The treatment was repeated every 3 weeks.. A total of 27 patients received six different S-1 dose levels. The dose-limiting toxicities (DLTs) were neutropenia, diarrhea, and vomiting. At dose level 5 (100 mg/m2), two patients experienced DLTs, while none of the third cohorts did. At dose level 6 (110 mg/m2), two patients experienced DLTs, and one of them died from treatment-related toxicity. The accrual was then stopped.. The recommended dose is S-1 100 mg/m2 on days 1-14, with 130 mg/m2 oxaliplatin on day 1, every 3 weeks. This regimen is proposed for the phase II study.

Topics: Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Recurrence; Tegafur; Treatment Outcome; Young Adult

Gemcitabine monotherapy or gemcitabine-containing combination chemotherapy is the standard first-line therapy for advanced pancreatic cancer. After disease progression, there is no standard regimen available. In a previous phase II trial, S-1 has been reported to show considerable efficacy, achieving a response rate of 37.5% in chemo-naïve patients with pancreatic cancer. This study evaluated the efficacy and toxicity of S-1 in patients with gemcitabine-refractory metastatic pancreatic cancer.. Eligibility criteria were histologically proven pancreatic adenocarcinoma with confirmation of progressive disease while receiving gemcitabine-based first-line chemotherapy, 20-74 years of age, Karnofsky performance status of 80-100 points, with measurable metastatic lesions, adequate hematological, renal and liver functions, and written informed consent. S-1 was administered orally at 40 mg/m(2) twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. The primary endpoint of this study was an objective response, and secondary endpoints included toxicity, progression-free survival (PFS) and overall survival, as well as clinical benefit response in symptomatic patients.. Forty patients from two institutions were enrolled between September 2004 and November 2005. The most common adverse reactions were fatigue and anorexia, although most of those adverse reactions were tolerable and reversible. One patient developed grade 3 pneumonitis without neutropenia and recovered with appropriate antibiotic treatment. Although no complete response was seen, partial response was obtained in six patients (15, 95% confidence interval, 3.9-26%). Stable disease was noted in 17 patients (43%), and progressive disease in 15 patients (38%). Out of 19 evaluable patients, a clinical benefit response was observed in four patients (21%). The median PFS was 2.0 months, and the median survival time was 4.5 months with a 1-year survival rate of 14.1%.. S-1 as monotherapy had marginal anti-tumor activity with tolerable toxicity in patients with gemcitabine refractory metastatic pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Tegafur

S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status.

Topics: Adult; Aged; Anemia, Hemolytic; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Fatigue; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Mitomycin; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The purpose of this study was to determine the optimal dose of oxaliplatin, when combined with a fixed dose of S-1 (40 mg/m twice daily on days 1-14) on a 3-week schedule, for patients with advanced and/or metastatic colorectal cancer. Patients were required to have a histologically proven advanced or metastatic colorectal cancer for which they had received no previous chemotherapy. Oxaliplatin was administered intravenously on day 1 every 3 weeks. Patients were divided into two groups to receive two doses of oxaliplatin - 100 mg/m or 130 mg/m. Ten patients were enrolled in the study between March 2006 and July 2006, and were followed up until 50% of the patients progressed. All patients were evaluated for chemotherapy-related toxicity. The maximum tolerated dose was not reached during the first course. One of six patients experienced grade 3 thrombocytopenia at dose level 2 of oxaliplatin. Nonhematological toxicity was mild and tolerable. During the full course of treatment, complete response was achieved in two of the nine evaluated patients and partial response was achieved in one patient. The remaining six patients achieved stable disease during first two courses of therapy, and four patients remained stable at the time of the last follow-up. The median time to progression-free survival was 8.3 months. When combined with a fixed dose of S-1 80 mg/m, oxaliplatin administered at a dose of 130 mg/m is tolerable and recommended for phase II study.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

This study evaluated the antitumor effect and safety of S-1, an oral fluoropyrimidine derivative, in patients with metastatic pancreatic cancer. Chemo-naive patients with pancreatic adenocarcinoma, and measurable metastatic lesions were enrolled. S-1 was administered orally twice daily after meals at a dose of 80, 100, or 120 mg/day for body surface areas (BSAs) of less than 1.25 m(2), between 1.25 m(2) and less than 1.5, or 1.5 m(2) or greater, respectively, for 28 consecutive days, followed by a 14-day rest. Fifteen (37.5%) of 40 patients responded to treatment, including 1 complete response and 14 partial responses. The median time to progression and the overall survival time were 3.7 months (95% confidence interval, 2.2-5.6 months) and 9.2 months (95% confidence interval, 7.5-10.8 months), respectively. The major adverse events were anorexia, fatigue, hemoglobin reduction, nausea and pigmentation change, although most were tolerable and reversible. Although disseminated intravascular coagulation occurred in two patients, the condition resolved with anticoagulant therapy. S-1 is an effective and well-tolerated drug. The effectiveness of this drug should be confirmed in a phase III study.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Survival Analysis; Tegafur

To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC).. Cisplatin was fixed at a dose of 60 mg/m2 on day 1 (D1) and the starting dose of S-1 was 60 mg/m2/day (30 mg/m2 bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 100 mg/m2/day (level V) unless the MTD was achieved.. Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m2/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m2/day (N=23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6-6.0 months) with a median OS of 10.0 months (95% CI, 5.1-14.8 months). Grade 3-4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%).. The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Fever; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Tegafur

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1-14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30-45 mg m(-2) b.i.d.) and docetaxel (25-40 mg m(-2)); MTD was 45 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel and RD was 40 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8-79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9-8.1) and 13.7 months (95% CI: 9.9-17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer.. Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended (D2) lymph-node dissection were randomly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only. In the S-1 group, administration of S-1 was started within 6 weeks after surgery and continued for 1 year. The treatment regimen consisted of 6-week cycles in which, in principle, 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks. The primary end point was overall survival.. We randomly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004. The trial was stopped on the recommendation of the independent data and safety monitoring committee, because the first interim analysis, performed 1 year after enrollment was completed, showed that the S-1 group had a higher rate of overall survival than the surgery-only group (P=0.002). Analysis of follow-up data showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The hazard ratio for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% confidence interval, 0.52 to 0.87; P=0.003). Adverse events of grade 3 or grade 4 (defined according to the Common Toxicity Criteria of the National Cancer Institute) that were relatively common in the S-1 group were anorexia (6.0%), nausea (3.7%), and diarrhea (3.1%).. S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer. (ClinicalTrials.gov number, NCT00152217 [ClinicalTrials.gov].).

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur

We conducted a phase II trial of gemcitabine with S-1, oral fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate, to evaluate the activity and toxicity of such a combination in metastatic pancreatic cancer (MPC) patients. Patients who had pathologically proven pancreatic cancer with metastatic lesions were eligible candidates for entry into the study. S-1 was given orally (30 mg m(-2)) b.i.d. for 14 consecutive days and gemcitabine (1000 mg m(-2)) was given on days 8 and 15. The cycle was repeated every 21 days. We enrolled 33 MPC patients. The median number of cycles was eight (range 1-20). Grade 3-4 toxicities were leucopenia (33%), neutropenia (55%), anaemia (9%), thrombocytopenia (15%), anorexia (6%), fever (9%), and interstitial pneumonia (6%). Objective responses were obtained in 16 patients (one complete response and 15 partial responses; response rate, 48%; 95% confidence interval (CI), 33-65). Median survival and 1-year survival rate were 12.5 months (95% CI, 5.9-19.1) and 54% (95% CI, 36-72), respectively. Combination chemotherapy with GEM and S-1 was well tolerated and yielded a significantly high response rate.

Topics: Aged; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Survival Analysis; Tegafur; Time Factors

The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer.. Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels: 800/60 (level 1), 1,000/60 (level 2), 1,000/70 (level 3) and 1,000/80 (level 4).. Eighteen patients were enrolled in this study. The maximum-tolerated dose was not reached even at the highest dose level (level 4) because only 2 of the 6 patients at this level experienced DLT. The DLTs were neutropenia and rash. Six (33%) of the 18 patients achieved a partial response and median overall survival time was 7.6 months.. Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer. We recommend a gemcitabine dose of 1,000 mg/m(2)/week and an S-1 dose of 80 mg/m(2)/day in further studies with this schedule.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease Progression; Drug Combinations; Female; Gemcitabine; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Pyridines; Tegafur; Time Factors; Treatment Outcome

A dose-escalation study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the dose-limiting toxicities (DLTs) in advanced gastric cancer.. Twelve patients were enrolled. S-1 was given orally at a fixed dosage of 40 mg/m(2) b.i.d. for 14 consecutive days, followed by a 1-week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8 at a dose of 50, 60, 70 or 80 mg/m(2), depending on the DLTs. Treatment was repeated every 3 weeks. A pharmacokinetic study was conducted in an additional 5 patients on days 7 and 8 during the first course given at the RD.. The MTD of paclitaxel was presumed to be 60 mg/m(2), because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). DLT was observed in 1 out of 8 patients at a dose of 50 mg/m(2). Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). The preliminary response rate was 62.5% (5/8) at the RD. There were no significant pharmacokinetic interactions between S-1 and paclitaxel. An adequate plasma paclitaxel concentration for an antineoplastic effect was achieved with weekly doses of 50 mg/m(2).. Weekly paclitaxel combined with S-1 was demonstrated to exhibit a tolerable toxicity profile with therapeutic plasma concentration at the dose of 50 mg/m(2). This regimen could represent a novel and low toxic combination for advanced gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Pyridines; Risk; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

The predictive values of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions were retrospectively evaluated in patients with gastric cancer treated by a regimen containing S-1. The study population consisted of 53 patients registered into different two phase II studies for metastatic gastric cancer; 27 patients treated by S-1-alone study: 26 patients treated with S-1 combined with irinotecan (CPT-11). TS and DPD gene expressions in primary tumours were measured by the real-time reverse transcription PCR method. There was no statistical difference in DPD gene expression in terms of response in cases treated with S-1 alone and those treated with S-1 plus CPT-11. TS mRNA of responding tumours was lower than that of nonresponding ones when treated with S-1 (P<0.005). In the S-1-alone group, taking TS cutoff as the median values, the response rate in the low TS group was 50%, but only 8% in the high TS group (P<0.05). Patients with low TS gene expression survived longer than those with high TS gene expression (P<0.0001). However, there was no statistically significant difference in response rate and survival between patients with low TS tumours and those with high TS tumours, when the cutoff was taken as the median value of TS gene expression in the group treated with S-1 plus CPT-11. In conclusion, treatment effects of S-1 monotherapy for gastric cancer were determined by the status of TS gene expression, regardless of DPD gene expression. TS predictive power was overcome by CPT-11 combination therapy with S-1.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Gene Expression Profiling; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Predictive Value of Tests; Prognosis; Pyridines; Stomach Neoplasms; Tegafur; Thymidylate Synthase; Treatment Outcome

S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoropyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer.. A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n=111) were enrolled, and 108 patients were regarded as eligible. S-1 was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times.. Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CR+PR) of 41.7% (95% confidence interval: CI, 32.3-51.5%). The incidences of toxicity (> or =grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group.. S-1 was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pyridines; Tegafur; Treatment Outcome

Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings. S-1 is a new oral fluorinated pyrimidine derivative. In a nonrandomized phase II study, patients with advanced/metastatic colorectal cancer were treated with S-1 at 40 mg m-2 b.i.d. for 28 consecutive days, repeated every 5 weeks, but by amendment the dose was reduced to 35 mg m-2 during the study because of a higher than expected number of severe adverse drug reactions. In total 47 patients with colorectal cancer were included. In the 37 evaluable patients there were nine partial responses (24%), 17 stable diseases (46%) and 11 patients had progressive disease (30%). Diarrhoea occurred frequently and was often severe: in the 40 and 35 mg m-2 group, respectively, 38 and 35% of the patients experienced grade 3-4 diarrhoea. The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations.

Topics: Aged; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pyridines; Tegafur; Treatment Outcome

This study set out to evaluate, in patients with metastatic colorectal carcinoma, the efficacy and toxicity of S-1, which contains tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate, based on a biochemical modulation of 5-fluorouracil (5-FU) targeted at inhibition of dihydropyrimidine dehydrogenase (DPD). Sixty-three patients with measurable metastatic colorectal carcinoma were enrolled into the study. None of the patients had received prior chemotherapy except for adjuvant setting. S-1 was administered orally twice daily at a standard dose of 80 mg m(-2) day(-1) for 28 days followed by a 14-day rest. This agent is continued until disease progression, unaccepted toxicity, or patient refusal. Twenty-two (35%) of the 62 eligible patients achieved PR with a 95% confidence interval of 25-48%. Five of the 10 patients with a history of adjuvant chemotherapy achieved partial remission. The median survival time was 12 months. Major adverse reactions included myelosuppressive and gastrointestinal toxicities, though their incidence of grade 3 or 4 being 13% in neutropenia and less than 10% in the others. None of the 53 patients treated as outpatients required hospitalization due to adverse reactions: These results suggest that S-1 achieves similar responses to those of infusional 5-FU plus leucovorin and shows the potential of another biochemical modulation with easily manageable toxicity.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Treatment Outcome

Background Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cisplatin; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Retrospective Studies; Tegafur

S-1, a 5-fluorouracil(5-FU) oral anti-cancer drug, has been traditionally used with a schedule of 4-week oral administration followed by 2-week rest for breast cancer treatment. We, herein, aimed to investigate the clinical efficacy and safety of a schedule of 2-week oral administration followed by 1-week rest for patients with metastatic breast cancer.. We enrolled patients with HER2-negative metastatic breast cancer who had not received prior chemotherapy. S-1 was administered consecutively for 2-weeks followed by a 1-week rest.. Between September 1, 2013 and August 31, 2016, 32 patients were enrolled. The median follow-up time was 32.1 months. The median progression-free survival (PFS) was 9.4 months. Overall survival (OS) was 41.0 months, time to treatment failure (TTF) was 7.8 months, response rate (RR) was 31.3%, and disease control rate (DCR) was 78.1%. The incidence of grade 3 side-effects was not high.. The 3-week schedule of S-1 can be considered useful as a treatment for patients with metastatic breast cancer, helping in maintaining a high quality of life.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

Although nivolumab treatment is effective in extending the overall survival (OS) in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), only a few patients benefit from this treatment. Recent studies have reported that chemotherapy and cetuximab might be effective for R/M HNSCC after nivolumab treatment. In the present study, we aimed to elucidate the effectiveness of chemotherapy after nivolumab treatment in patients with R/M HNSCC.. This retrospective study included 10 patients with R/M HNSCC who were mainly treated with paclitaxel plus cetuximab (7/10, 70%) or S-1 (3/10, 30%) following nivolumab treatment. Chemotherapy was administered as a second-line or higher palliative treatment. The performance status of all patients ranged from 0 to 2. The progression-free survival (PFS) was analyzed using the Kaplan-Meier method.. The response rate (RR), clinical benefit rate, and median PFS were 60%, 90%, and 5.4 months, respectively. Regarding adverse effects, Grade 3 neutropenia and hypomagnesemia due to salvage chemotherapy administered after immunotherapy were observed in one patient. The treatment significantly increased the RR compared to that achieved with other palliative chemotherapies reported so far.. A higher RR and clinical benefit rate were observed for our strategy than for any first-line regimen, suggesting that our strategy might improve the PFS. Palliative chemotherapy with/without cetuximab after nivolumab treatment might be useful in patients with R/M HNSCC. Although the results of this retrospective study are limited, this strategy can be a good treatment option for patients with R/M HNSCC because of its strong clinical benefits and acceptable toxicity.

Topics: Adult; Aged; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Nivolumab; Oxonic Acid; Paclitaxel; Palliative Care; Progression-Free Survival; Retrospective Studies; Salvage Therapy; Squamous Cell Carcinoma of Head and Neck; Tegafur; Treatment Failure

We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer (AGC) and the role of mutational analysis of circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire in predicting clinical outcomes.. Consecutive patients (. The DC-CIK infusions were well tolerated with no serious adverse events. The disease control rates (CR. DC-CIK combined with S-1 plus cisplatin provided a favorable PFS and OS in patients with AGC and the combination therapy was safe with tolerable toxicities. Clinical efficacy correlated with decreases in ctDNA mutational profiles and restored TCR repertoire.

Topics: Aged; Antimetabolites, Antineoplastic; Biomarkers; Combined Modality Therapy; Cytokine-Induced Killer Cells; Dendritic Cells; Drug Combinations; Female; Humans; Immunotherapy; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prospective Studies; Retreatment; Stomach Neoplasms; Tegafur; Treatment Outcome

Apatinib, one of the novel oral antiangiogenic agents, shows survival benefits in treating advanced or metastatic gastric adenocarcinoma. However, its efficacy in treating advanced head and neck neoplasms has not been reported. Herein, three elderly men with advanced head and neck neoplasms were treated with apatinib and S-1. Their initial diagnoses were hypopharyngeal carcinoma, metastatic squamous cell carcinoma of head and neck, and squamous cell carcinoma of the pyriform sinus. All patients underwent repeated chemotherapy but developed disease progression. As they refused radiotherapy due to its serious adverse reaction, apatinib was administered at a dose of 425 mg daily and S-1 at 60 mg twice daily. Thirty days after apatinib administration, the patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors 1.1 standard. Mild toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib and S-1 could be the new treatment option for advanced head and neck neoplasms. However, clinical trials are required to confirm their efficacy and safety.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Biopsy; Drug Combinations; Head and Neck Neoplasms; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Pyridines; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

While some studies show improved outcomes in clinical trial participants as compared to non-participants, existence of such a trial effect has not been proved precisely.. This was a prospective cohort study to compare the prognoses for participants in the randomized controlled trial (SELECT BC) and non-participants. SELECT BC compared S-1 and taxane as first-line treatment for metastatic breast cancer. Non-participants were all patients who met the eligibility criteria of SELECT BC and who had been requested to participate in that trial by attending doctors and declined. The study aimed to compare the prognoses between participants and non-participants. The primary endpoint was median overall survival.. The median OS in participants was significantly superior to that in non-participants with a statistically significant difference (36.8 months vs. 25.2 months. HR 1.48, p = 0.022). A similar result was obtained when only patients who received the same chemotherapy (S-1 or taxane) used in SELECT BC after declining participation were assumed as non-participants (36.8 months vs. 22.0 months. HR 2.03, p = 0.006).. This study may suggest the existence of a trial effect, in which, for a given treatment, participation in a clinical trial is associated with a better outcome.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Bridged-Ring Compounds; Combined Modality Therapy; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Outcome Assessment, Health Care; Oxonic Acid; Patient Participation; Randomized Controlled Trials as Topic; Survival Rate; Taxoids; Tegafur; Treatment Outcome

To investigate the treatment effects of gemcitabine plus S-1 (GS) for metastatic pancreatic cancer in our institution.Data from 41 patients with metastatic pancreatic cancer treated with GS regimen in West China Hospital, Sichuan University were reviewed. The therapeutic efficacy and toxicity were evaluated. The influencing factors of progression-free survival (PFS) and overall survival (OS) were also explored.At the last follow-up, all patients had died. The objective response rate was 22.0% (9/41) and the disease control rate was 65.9% (27/41). The median PFS and OS times were 5.1 (range, 1.5-21) and 10.6 months (range, 1.5-40), respectively. The 0.5-, 1-, and 2-year OS rates were 65.9%, 41.5%, and 9.8%, respectively. In multivariate analysis, body mass index and carbohydrate antigen 19-9 change were the significant influencing factors of PFS, compared to tumor site and chemotherapy cycles for OS. The adverse effects were moderate and tolerable.The effects of GS for metastatic pancreatic cancer in our institution were good. The adverse effects were moderate and tolerable. However, further investigation in future prospective clinical studies is warranted.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; China; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Tegafur

A 62-year-old Japanese female with primary lung adenocarcinoma received seven cycles of nivolumab as an eighth line of chemotherapy until she presented with hemoptysis. After transcatheter arterial embolization therapy, she received subsequent chemotherapy with paclitaxel and S-1. Four weeks later, a chest computed tomography examination revealed infiltrative shadows mainly in the right lung field, in addition to enlargement of the lung metastasis in the right middle lung lobe. Bronchofiberscopic examination revealed infiltration of lymphocytes without any malignant cells in the right segment 1 of the lung, which suggested interstitial lung disease. Corticosteroid therapy not only improved the infiltrative shadows but also reduced the lung metastasis. Even after the infiltrative shadows improved, the lung metastasis reduced further. This phenomenon resembles manifestation of pseudoprogression during treatments with immune checkpoint inhibitors, such as nivolumab.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antibodies, Monoclonal; Drug Combinations; Female; Humans; Lung; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Nivolumab; Oxonic Acid; Paclitaxel; Tegafur; Tomography, X-Ray Computed

Three randomised trials (GEST, JACCRO PC-01, and GEMSAP) were conducted to evaluate the efficacy of gemcitabine plus S-1 (GS) vs gemcitabine alone in patients with advanced pancreatic cancer (PC). In this pooled analysis, the efficacy and safety of GS vs gemcitabine were evaluated.. Additional follow-up was conducted and survival data were updated in each study. A total of 770 patients (gemcitabine 389; GS 381) were included in the pooled analysis. The efficacy and safety data were analysed according to disease extent: locally advanced PC (LAPC) or metastatic PC (MPC).. There were 738 (95.8%) overall survival events. In patients with LAPC (n=193), the median survival was 11.83 months for gemcitabine and 16.41 months for GS (hazard ratio (HR)=0.708; 95% confidence intervals (CI), 0.527-0.951; P=0.0220). In patients with MPC (n=577), the median survival was 8.02 months for gemcitabine and 9.43 months for GS (HR=0.872; 95% CI, 0.738-1.032; P=0.1102). The rate of grade 3/4 toxicity (rash and thrombocytopenia in LAPC; rash, diarrhoea, vomiting, and neutropaenia in MPC) was significantly higher for GS than for gemcitabine.. Gemcitabine plus S-1 is a viable treatment alternative to gemcitabine, which is one of the standard treatments in patients with LAPC.

Topics: Aftercare; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Deoxycytidine; Diarrhea; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate; Tegafur; Thrombocytopenia; Vomiting

We retrospectively investigated the efficacy and safety of S-1 and oxaliplatin(SOX)as the first-line chemotherapy in patients with metastatic/recurrent gastric cancer. A total of 27 patients who received SOX as the first-line chemotherapy in our hospital were considered for the study. The SOX chemotherapy schedule consisted of 1 course every 3 weeks. S-1 was administered orally, at 80-120mg-body, every day for 14 days. Oxaliplatin was infused at 100mg/m2 on day 1 of each course. The median number of treatment courses was 7. The response rate and disease control rate were 47.6% and 76.2%, respectively. The observed adverse events of Grade 3 or more included neutropenia(33.3%); peripheral neuropathy and anorexia(11.1%); thrombocytopenia(7.4%); and anemia, diarrhea, fatigue, and hypercalcemia(3.7%). The median overall survival was not achieved, and the 1-year survival rate was 63.2%. Therefore, SOX is an effective and feasible first-line chemotherapy that is easily available for ambulatory treatment of patients with metastatic/recurrent gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Recurrence; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC.. We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group).. The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05).. The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Humans; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Second Primary; Oxonic Acid; Survival Analysis; Tegafur

This study evaluated the cost-effectiveness of replacing standard intravenous therapy (taxane) with oral S-1 therapy for first-line metastatic breast cancer treatment.. This cost-effectiveness analysis was based on data from a randomized phase III trial (SELECT BC). As cost-effectiveness was a secondary endpoint of the SELECT BC trial, some of the randomized patients participated in an EQ-5D survey (N = 391) and health economic survey (N = 146). The EQ-5D responses, claims, and prescription data were collected for as long as possible until death. The expected quality-adjusted life years (QALY) obtained from each treatment were calculated using patient-level EQ-5D data, and the expected cost was calculated using patient-level claim data. The analysis was performed from the perspective of public healthcare payers.. The estimated EQ-5D least-square means and 95% CI up to 48 months were 0.764 (95% CI, 0.741-0.782) and 0.742 (95% CI, 0.720-0.764) in the S-1 and taxane arms, respectively. The expected QALY was 2.11 for the S-1 arm and 2.04 for the taxane arm, with expected costs of JPY 5.13 million (USD 46,600) and JPY 5.56 million (USD 50,500), respectively. These results show that S-1 is cost-saving. According to probabilistic sensitivity analysis, S-1 was dominant with a probability of 63%. When the willingness to pay (WTP) value was JPY 5 million (USD 45,500) per QALY, the probability of being cost-effective was 92%.. Our results show that the introduction of oral S-1 therapy for metastatic breast cancer is highly likely to be cost-effective.. UMIN CTR C000000416 . Registered on May 10, 2006.

Topics: Antimetabolites, Antineoplastic; Biomarkers, Tumor; Breast Neoplasms; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Drug Combinations; Female; Humans; Japan; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Tegafur; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Remission Induction; Stomach Neoplasms; Tegafur

This study was designed to compare the efficacy and safety of paclitaxel/oxaliplatin/fluorouracil (TOF) regimen and S-1/oxaliplatin (SOX) regimen for metastatic gastric cancer (GC) patients.. Sixty patients were divided into TOF group and SOX groups randomly. Patients in the TOF group received paclitaxel (135 mg/m2 iv) on day 1, oxaliplatin (100 mg/m2 iv) on day 1, fluorouracil (500 mg/m2 continuous iv) on day 1-5. The patients in the SOX group received oxaliplatin (130 mg/m2 iv) on day 1 and S-1 (40 mg~60mg orally twice/day based on body surface area) on days 1-14. All the treatments were repeated every 21d for 4-6 cycles.. The ORR and DCR of TOF group was 43.3% and 60.0%, respectively while that of SOX group was 36.7% and 56.7%. There were no statistical differences between the ORRs (χ2 = 0.278) and the DCRs (χ2 = 0.069) of the 2 groups. The majority of adverse events of two groups were hematological and digestive ones. Most of them were grade I and II. The adverse event rate of TOF group was higher than SOX group. The PFS times of TOF and SOX groups were 6.5 and 5.8 months, respectively. There was no statistical difference between the PFSs of the 2 groups (P = 0.451).. The efficacies of TOF and SOX regimens are similar but the safety of SOX regimen better than TOF regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.. Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.. Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.. Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur; Tomography, X-Ray Computed

Thymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis.. We assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort.. A total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4-67.4) and the disease control rate was 85.7 % (60.0-96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6-12.2 months), and median overall survival was 30.0 months (range, 6.2-41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed.. S-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers; Disease Progression; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Gene Expression; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Recurrence; Retrospective Studies; RNA, Messenger; Tegafur; Thymus Neoplasms; Treatment Outcome; Young Adult

This study was aimed to assess the feasibility and short-term outcomes of adjuvant systemic chemotherapy with either S-1/oxaliplatin (SOX) or mFOLFOX6 (FOLFOX)after curative resection of distant metastases from colorectal cancer. We retrospectively examined 16 patients who underwent R0 resection of colorectal metastases, including the liver (n=6), lung (n=5), lymph node (n=3), and peritoneum (n=2), followed by chemotherapy with SOX (n=7) or FOLFOX (n=9) until disease progression. The mean recurrence-free survival was 13.2 months in the SOX group and 16.9 months in the FOLFOX group. The mean overall survival was 17.9 and 22.9 months, respectively. The number of given courses were 6.5 and 11.0, respectively. Although sensory neuropathy was observed in 38% of the patients, relative dose intensity was higher than 80%. Adjuvant chemotherapy with SOX or FOLFOX was feasible and effective. Further randomized prospective trials are warranted to confirm these results.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Recurrence; Retrospective Studies; Tegafur

To observe the short-term efficacy and safety of S-1 combined with cisplatin (DDP) chemotherapy for advanced gastric cancer (AGC).. Sixty-six patients were diagnosed with AGC and were admitted to our department from February 2012 to January 2015 and retrospectively analyzed. Of these patients, 31 (experimental group) underwent S-1 combined with DDP chemotherapy and 35 received oxaliplatin combined with tegafur and calcium folinate chemotherapy regimen (control group). The chemotherapy regimen for the experimental group included S-1, 60 mg bid on d1-d14 and 60 mg/m 2 DDP by intravenous dripping on d1-d3, with 4 weeks in a cycle. The chemotherapy regimen for the control group consisted of 130 mg/m 2 oxaliplatin by intravenous dripping, d1; 600 mg/m 2 tegafur by intravenous dripping on d1-d5; and 120 mg/m 2 calcium folinate by intravenous dripping on d1-d5, with 3 weeks in a cycle. The efficacies and adverse effects of the two regimens were assessed after three cycles.. After three cycles, the objective response rates of the experimental and control groups were 41.94% and 42.86%, without significantly difference (P > 0.05), respectively. However, the incidence rate of adverse drug reactions in Grades 3-4 in the experimental group was significantly lower than that of control group (P < 0.05).. The short-term efficacy of primary S-1 with DDP chemotherapy for AGC is relatively satisfactory with less adverse effects.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment in elderly patients with advanced gastric cancer. One hundred and twenty-nine patients with recurrent or metastatic gastric adenocarcinoma were treated with SOX; S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily on days 1 to 14 followed by a 7-day rest period, 130 mg/m(2) oxaliplatin was given as an intravenous infusion over 2-hours on day one. The cycle was repeated every three weeks. All of the patients were older than 65 years. Among 129 patients enrolled, nine patients could not be evaluated for responses because of the absence of any measurable lesions or early discontinuation of therapy. Assessment of the response of 120 patients was made. The overall objective response rate was 54.2 % (95 %CI, 45.3-63.1 %), with three complete responses and 62 partial responses. The disease control rate was 80.8 % (95 %CI, 73.8-87.8 %). The median follow-up period was 23 months (range, 5-42 months). The median time to progression was 6.9 months (95 %CI, 5.5-8.3 months) and the median overall survival was 12.8 months (95 %CI, 11.4-14.2 months). The one-year survival rate was 57.5 % (95 %CI, 48.7-66.3 %). In 129 patients assessed safety, grade 3 and 4 toxicities included leucopenia (20.9 %), neutropenia (24.0 %), anemia (10.9 %), thrombocytopenia (10.1 %), anorexia (3.1 %), peripheral neurotoxicity (15.5 %), and fatigue (12.4 %). No treatment-related deaths occurred. Combination chemotherapy with SOX offers an effective, safe and well-tolerated regimen for elderly patients with advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Tegafur

Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy.. The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently.. Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed.. The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.

Topics: Adult; Aged; Anthracyclines; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Tegafur

Chemotherapy for unresectable pancreatic cancer should not only prolong survival but maintain quality of life, considering its limited life expectancy. To achieve these goals, biweekly gemcitabine plus S-1 was assessed in the clinical practice setting.. Fifty-two patients with either locally advanced or metastatic pancreatic cancer who received biweekly gemcitabine plus S-1 as a first-line anti-cancer treatment were included in this study. Treatment delivery, toxicity, response, and survival were reviewed to assess the feasibility and efficacy.. The completion rate of treatment delivery was 95.1%, with relative dose intensity of 97.1% for gemcitabine and 97.3% for S-1. Overall, grade 3 or worse adverse events were rare, with hematologic toxicities occurring in 5.8%. The objective response rate was 30.8%, and more than a 50% reduction of CA19-9 was observed in 77.1%. Surgical conversion was completed with a margin-negative resection in four patients whose tumor had shrunk for at least 6 months. The median progression-free and overall survivals were 10.4 and 18.2 months, respectively. Reduction of CA19-9 was associated with longer survival.. Biweekly gemcitabine plus S-1 may be a good alternative to current standard chemotherapies for unresectable pancreatic cancer with less toxicity and less treatment burden without losing efficacy.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Feasibility Studies; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Tegafur; Treatment Outcome

Chemotherapy with S-1 and oxaliplatin is a new treatment for metastatic colorectal cancer. We present the first case of S-1, oxaliplatin, and bevacizumab therapy in our hospital. The patient was a 69-year-old woman with ascending colon cancer and multiple lung and liver metastases. She tended to suffer from constipation; stenoses at the cecum and colon cancer were detected by colon fiberscopy. Following surgical resection of the primary tumor, the patient received systemic chemotherapy with S-1, oxaliplatin, and bevacizumab. Following chemotherapy, CT showed no cancer in the lung and cancer reduction in the liver or dissemination. The patient had diarrhea and no appetite at first, so we reduced the oxaliplatin dose by 80%. After reduction of the oxaliplatin dose, we could treat the patient with S-1 and oxaliplatin continuously with no toxicity. S-1 and oxaliplatin chemotherapy is cost-effective, and has less toxicity than other chemotherapies, if proper measures are taken. It seemed to have a non-inferior response rate and disease control compared to other chemotherapies, such as FOLFOX. Thus, this chemotherapy is a valid choice for metastatic colorectal cancer.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Fatal Outcome; Female; Humans; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

To clarify the tolerance and pharmacokinetics of combined therapy with S-1 and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic or recurrent breast cancer.. From January 2008 through to September 2009, combined therapy with S-1 and trastuzumab was given to 7 patients with HER2-positive metastatic or recurrent breast cancer. The incidence of adverse events and the pharmacokinetics of tegafur, 5-fluorouracil, and gimeracil in plasma were studied.. One patient had grade 3 leukopenia, and another had a grade 3 elevation of alanine aminotransferase. All other adverse events were grade 2 or lower. The combination of S-1 and trastuzumab did not cause any new adverse events. The incidence of adverse events was similar to those associated with S-1 alone. The median number of treatment cycles was 11. The pharmacokinetics of tegafur, 5-fluorouracil, and gimeracil after treatment with S-1 plus trastuzumab did not markedly differ from those after S-1 alone.. Combined therapy with S-1 and trastuzumab did not cause any new adverse events, administration continuity was good, and the therapy was well tolerated.

Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Feasibility Studies; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Receptor, ErbB-2; Tegafur; Trastuzumab

We investigated effects of gemcitabine-based adjuvant chemotherapy (GEM) on prognosis of patients with gallbladder cancer.. We retrospectively analyzed outcomes of 36 patients who underwent radical resection for gallbladder cancer from 2001 through to 2012, using χ(2) for prognostic factors and Kaplan-Meier estimator and log-rank tests for survival data.. The GEM group had higher rates of lymph node positivity and distant metastasis, higher UICC stage and fewer R0 resections; their 5-year survival rate (60%) did not significantly differ from that of the controls (70.0%), nor was GEM a significant prognostic factor in univariate analysis. However, among patients who underwent R1 and R2 resections, GEM significantly improved prognosis in both univariate and multivariate analyses. Median survival of the R1/2 GEM group (66.4 months) was significantly better than that of controls (5.4 months) (p=0.002).. GEM improved prognosis of patients with gallbladder cancer after R1/R2 resections.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Chemotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gallbladder Neoplasms; Gemcitabine; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Survival Rate; Tegafur

This retrospective study evaluates the efficacy and safety of S-1 chemotherapy for recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy.. Thirty-nine patients with recurrent and metastatic nasopharyngeal carcinoma who failed previous platinum-based chemotherapy received oral S-1 chemotherapy (twice daily from day 1 to 14) every 3 weeks. The dose of S-1 was determined according to the body surface area (BSA): 40 mg twice a day for BSA <1.25 m(2); 50 mg twice a day for 1.25 m(2) ≤BSA<1.5 m(2); and 60 mg twice a day for BSA ≥1.5 m(2).. Treatment was well tolerated. Most adverse events were mild. Grade 3 hematological toxicity occurred in 7.7%. There was one complete response (2.6%) and 12 partial responses (30.7%), giving an overall response rate of 33.3% (95% CI [confidence interval], 21.7-50.8). Median time-to-progression was 5.6 months, and median survival was 13.9 months. One- and 2-year survival rates were 60% and 26%, respectively.. S-1 monotherapy is considered a safe and effective treatment option for recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma; Disease Progression; Drug Combinations; Female; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Platinum Compounds; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome

TS-1, an oral fluoropyrimidine, is known to be effective for the treatment of various carcinomas including advanced/metastatic breast cancer.The Kumamoto Breast Cancer Cooperative Group(KBCCG)conducted an observational study, wherein, the efficacy and safety of TS-1 monotherapy was analyzed in 35 patients with recurrent or metastatic breast cancer.The median time to cancer progression was 3.7 months, overall response rate was 12%, and clinical benefit rate was 32%. Adverse events were observed in 27 patients(77%), and adverse events of Grade >3 were observed in 7 patients(20%). The rate of treatment-related Grade 3 and 4 adverse events increased, and was associated with poor levels of creatinine clearance(Ccr)ie <60mL/min.This study suggests that TS-1 monotherapy can potentially be used as a salvage treatment for advanced/metastatic breast cancer owing to its safety and efficacy.Measuring the level of Ccr before TS-1 therapy should be considered to avoid severe adverse events.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur

The safety of S-1 in recurrent colorectal cancer patients with chronic myeloid leukemia (CML) treated with dasatinib has not been established. We evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with CML treated with dasatinib.. A 70-year-old man had undergone surgery three times for sigmoid colon cancer and recurrence. Systemic chemotherapy with S-1 plus oxaliplatin plus bevacizumab as a clinical trial had already been administered because of metastatic colon cancer. The patient's medical history was CML, and he had been receiving dasatinib treatment (100 mg once daily). Based on the diagnosis of unresectable and multiple metastases, S-1 monotherapy was started. S-1 (120 mg/day) was taken for 28 consecutive days, followed by a 14-day rest. Blood samples were obtained before and after the first administration of S-1. The plasma pharmacokinetics of S-1 were comparable to a pharmacokinetics study of S-1.. The area under the plasma concentration-time curve (AUC0-8) of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), oxonate (Oxo), and 5-fluorouracil (5-FU) was 4,309.2, 716.3, 86.8, and 492.75 ng h/mL, respectively, after S-1 administration. The pharmacokinetics of FT, CDHP, Oxo, and 5-FU after treatment with S-1 were not significantly different from a phase I pharmacokinetics study of S-1. During treatment with S-1 and dasatinib, CML relapse and serious myelosuppression were not observed.. Our report suggests that S-1 is an important treatment option for recurrent colorectal cancer in patients with CML treated with dasatinib.

Topics: Aged; Antimetabolites, Antineoplastic; Area Under Curve; Colonic Neoplasms; Dasatinib; Drug Combinations; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Protein Kinase Inhibitors; Pyrimidines; Tegafur; Thiazoles

Tegafur-gimeracil-oteracil potassium (TS-1)is a drug that is used mainly as a third-line treatment or beyond for metastatic breast cancer(MBC). However, there is still insufficient evidence on its clinical effectiveness, and there are very few reports on clinical research using TS-1 up front. In this report, we examined the effectiveness and safety of TS-1 therapy for MBC.. The subjects were 46 patients with MBC who were treated with TS-1 between January 2005 and January 2013. These patients were retrospectively examined.. The objective response rate to TS-1 therapy was 30.4%, clinical benefit rate (CBR)was 50.0%, and the median time to treatment failure was 10.7 months. When examined by site, the CBR was high locally (46.2%), in the lymph nodes (40.7%), in the bone (42.9%), and in the lungs and pleura (44.8%). However it was low in the liver(30.0%). The relationship was examined between clinicopathological factors and the effectiveness of TS-1 therapy. The objective response rate (ORR) was significantly higher for patients with disease-free interval (DFI) of 2 years or more (p=0.039), TS-1 therapy used as third-line treatment or earlier (p=0.022), negative HER2 status (p=0.020), and no history of capecitabine (CAP)therapy (p=0.049). The CBR was significantly higher for patients with no visceral metastasis (p=0.032), TS-1 used as third-line treatment or earlier (p=0.019), negative HER2 status (p= 0.045), no history of CAP therapy (p=0.006), and no history of tegafur-uracil/doxifluridine therapy (p=0.031). Multivariate analysis showed that DFI of 2 years or more (p=0.035, odds ratio:0.104)was an independent predictor of effectiveness assessed by ORR. There were only 4 patients in whom the treatment was discontinued due to adverse event, and TS-1 was generally well tolerated.. TS-1 was highly effective and well tolerated by patients with MBC. Its up-front use might enable the maintenance of satisfactory QOL and the enhancement of its clinical effectiveness.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pyridines; Retrospective Studies; Tegafur

To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM).. A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter.. Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the response evaluation criteria in solid tumors criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date.. Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Fluorouracil; Glycosylation; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

Ten patients aged 75 years or more with advanced or metastatic gastric cancer were prescribed S-1 plus docetaxel (DOC) combination therapy. None of the patients showed complete response, but 2 showed partial response and 4 showed stable disease. Grade 3 or 4 toxicities occurred in 3 patients. Three patients with performance status (PS) 1 achieved partial response or stable disease and were free of Grade 3 or 4 toxicities, whereas the response and occurrence of adverse events in 7 patients with PS 2 varied widely. In these patients, an investigation of the relationship between response to treatment and the Vulnerable Elders Survey (VES-13) score showed that VES-13 scores were higher in the non-response group than in the other patients and in patients who experienced adverse events than in those who did not. These findings suggest that VES-13 could be a useful screening tool for predicting response and the occurrence of adverse events in elderly patients undergoing combined S-1 plus DOC therapy for advanced or metastatic gastric cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Data Collection; Docetaxel; Drug Combinations; Female; Humans; Male; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

In the present study, we evaluated the outcome of preoperative treatment with S-1 and CDDP for the treatment of advanced gastric cancer. Fifty-five cases of advanced gastric cancer received pre-operative treatment with S-1 and CDDP. The tumor control rate( PR and CR according to RECIST criteria) was 55%. The clinical response and histological response to the treatment and curative resection were closely related to favorable postoperative survival. We noted that patients who demonstrated CR or PR received S-1 as postoperative treatment, whereas those with SD or PD were more likely to receive paclitaxel as postoperative treatment. Preoperative treatment with S-1 and CDDP was not only an effective initial treatment, but also demonstrated favorable results in a S-1 in vivo sensitivity test.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Humans; Neoadjuvant Therapy; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Prognosis; Stomach Neoplasms; Tegafur

Combination chemotherapies of oxaliplatin or irinotecan with fluoropyrimidine and molecular target drug were reported to be active in several clinical studies and so regarded as a first-line standard therapy for unresectable or metastatic colorectal cancer. However, the incidence of adverse events is not so low. We investigated the efficacy and safety of chemotherapy combined bevacizumab with fluoropyrimidine as a first-line treatment for frail patients.. Twenty-six patients with unresectable or metastatic colorectal cancer who were treated with first-line chemotherapy combined bevacizumab with S-1 or 5FU/LV (modified Roswell Park Memorial Institute regimen) at our hospital between October 2007 and December 2010 were retrospectively investigated.. The median age was 72 years (range 66-84). Performance status was 0, 1 and 2 in 8, 17 and 1 patient, respectively. The primary lesion was located in the colon in 14 patients and in the rectum in 12. Twenty patients were with resection of the primary lesion and 6 were without, 8 were with postoperative adjuvant chemotherapy and 18 were without. The number of metastasized organs was 1, 2 and 3 in 17, 9 and 0 patients, respectively. The liver, lung, lymph node and peritoneum were metastasized in 9, 9, 11 and 5 patients, respectively. The KRAS gene was wild in 11, mutated in 7 and unknown in 8 patients. Bevacizumab with S-1 was used in 17 patients and bevacizumab with 5FU/LV was used in 9. Response and disease control rates were 50 and 100%, respectively. The median duration of progression-free survival was 9.1 months and the median time to treatment failure was 9.0 months. The incidences of all grades of neutropenia and hypertension were 31%, those of grade 3 or severer were 12%, and those of other adverse events were low. Grade 3 cerebral hemorrhage, grade 4 pulmonary embolism and grade 5 febrile neutropenia each occurred in 1 patient.. The first-line chemotherapy combined bevacizumab with fluoropyrimidine for frail patients with unresectable or metastatic colorectal cancer in Japan was comparable to the safety and efficacy of combination therapy reported previously in Western countries.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Female; Fluorouracil; Frail Elderly; Humans; Leucovorin; Male; Neoplasm Metastasis; Oxonic Acid; Retrospective Studies; Tegafur; Treatment Failure; Vascular Endothelial Growth Factor A

Although chemotherapy consisting of cisplatin and 5-fluorouracil(CF)has been a standard regimen for esophageal cancer, it might be difficult to use continuously. This study evaluated the response and safety of docetaxel plus S-1 used as a second line therapy. We reviewed 21 patients(postoperatively, 11; after definitive chemoradiotherapy, 8; after chemotherapy, 2) who received chemotherapy between 2006 and 2010. Metastatic or recurrent disease was detected in the organs(n=8), lymph nodes(n=8), main tumors(n=3), mediastinum(n=1), and pleura(n=1). Docetaxel 30mg/m2 was infused every 2 weeks, and S-1 80mg/m2 was taken for 2 weeks, then with 2 weeks rest until progression. Almost all of the patients received docetaxel in the outpatient chemotherapy room. The median number of treatment cycles was 3, ranging from 1-12. Among the 14 patients with a therapeutic response, three(21%)achieved PR, 8 showed SD, and 3 had PD. Toxicity which included grade 3/4 was neutropenia in 6 patients, and anemia in one patient. After a follow-up of over one year, the median overall survival was 10 months, and the one-year survival rate was 38%. Docetaxel plus S-1 might be a feasible regimen as a second-line chemotherapy for metastasis or recurrence of esophageal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Recurrence; Salvage Therapy; Taxoids; Tegafur

A 46-year-old woman with lower abdominal distension was diagnosed as gastric cancer in our hospital. She had multiple metastases of lungs, lymph nodes, bilateral ovaries, and uterus. After she underwent sub-total gastrectomy, bilateral oophorectomy, and total hysterectomy, she received adjuvant chemotherapy followed by docetaxel and S-1. After 6 courses of chemotherapy, PET/CT revealed no recurrences (complete response), and she was therefore administered S-1 for only 6 months. She has remained without recurrence 15 months after the operation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Positron-Emission Tomography; Remission Induction; Stomach Neoplasms; Taxoids; Tegafur

S-1 plus cisplatin is the standard first-line chemotherapy for metastatic gastric cancer (MGC) in Japan, but the relationship between dose intensity and antitumor effects remains unclear.. We retrospectively studied 64 patients who received S-1 plus cisplatin for MGC from January 2006 to December 2010 in two Japanese hospitals.. The median relative dose intensity (RDI) of S-1 plus cisplatin was 87% (range, 59.5%-100%). The cut-off value of RDI of S-1 plus cisplatin was identified to be 80% by a receiver operating characteristic analysis of the tumor response. In the RDI<80% (n=19) and the RDI≥80% (n=45) groups, the response rates were 20.0% and 37.5% (p=0.182), the median survival times were 394 and 376 days (p=0.915), and the median progression-free survival (PFS) was 188 and 170 days (p=0.851), respectively.. An appropriate RDI reduction may be permitted for patients with MGC in palliative settings.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; ROC Curve; Stomach Neoplasms; Tegafur

To assess the clinical activity and toxicity of a combination chemotherapy regimen of S-1 and cisplatin in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) in a retrospective study.. A total of 49 patients were treated in an outpatient setting with S-1 80 mg/m(2) on days 1-14 and with cisplatin 70 mg/m(2) on day 1 every 3 weeks for a maximum of six cycles as a first-line palliative chemotherapy. Patients who achieved complete response (CR), partial response (PR) or stable disease (SD) after six cycles received S-1 monotherapy as a maintenance therapy.. The median patient age was 55 years (range 33-79), 89.8 % were male, and the Eastern Cooperative Oncology Group performance status distribution was 0/1/2 (20.4 %/73.5 %/6.1 %). Of the 43 evaluable patients, 2 (4.1 %) achieved CR and 20 (40.8 %) had a PR, for an overall response rate of 44.9 %. Thirteen patients (26.6 %) had SD. The median number of chemotherapy treatments was 4 (range 1-18). Nine patients received maintenance S-1 monotherapy after six cycles of combination chemotherapy. With a mean 10.5 months (range 1.3-25.1) of follow-up, the median progression-free and overall survival were 4.5 (95 % CI, 3.7-5.3 months) and 10.8 months (95 % CI, 5.9-15.6 months), respectively. The main grade 3-4 toxicities were neutropenia (37 %), anemia (16 %) and general weakness (8 %). Other toxicities, including nausea/vomiting, mucositis and neuropathy, were mostly grade 1-2 and easily manageable.. The combination of S-1/cisplatin therapy had a favorable efficacy with manageable toxicity as a first-line chemotherapy regimen for advanced head and neck squamous cell carcinoma patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Squamous Cell Carcinoma of Head and Neck; Tegafur

Radiation Therapy Oncology Group study 91-11 found that in resectable advanced laryngeal cancer, the locoregional control rate achieved with reduced intra-arterial cisplatin and concurrent radiotherapy (RADPLAT) was comparable to that of a concurrent chemoradiotherapy arm, with reduced toxicities. However, distant metastases were more frequent. Our study retrospectively evaluated the efficacy and feasibility of adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for distant metastases following reduced RADPLAT.. We analyzed 61 patients who were treated with reduced RADPLAT and achieved a complete response at the primary site. After the use of reduced RADPLAT, 24 patients were administered S-1 for 2 weeks followed by 1 week of rest, and the cycle was repeated for 6 months (S-1+ group). Thirty-seven patients were not administered S-1 (S-1-group).. The hazard ratio for distant metastases in the S-1+ group was 0.114 (95% confidence interval, 0.015 to 0.881; p = 0.0374). There was a significant difference in disease-free survival in favor of the S-1+ group (p = 0.0455). Nineteen patients (79.2%) in the S-1+ group received S-1 according to the planned schedule and dose. Grade 3 toxicities were observed in 2 patients (8.3%), but there was no grade 4 event.. In resectable advanced laryngeal cancer, S-1 adjuvant chemotherapy is an effective and feasible treatment option to control distant metastases following reduced RADPLAT.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Humans; Laryngeal Neoplasms; Larynx; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organ Sparing Treatments; Oxonic Acid; Radiation-Sensitizing Agents; Radiotherapy Dosage; Radiotherapy, Adjuvant; Retrospective Studies; Tegafur

A 61-year-old man exhibiting epigastric malaise on hunger was diagnosed with early gastric cancer by upper gastrointestinal endoscopy. Since no obvious metastasis was recognized by abdominal computed tomography(CT), he underwent distal gastrectomy with D1+ lymphadenectomy. Histopathological examination revealed a pStage IA lesion[pT1a (m), pN0]. He received no adjuvant chemotherapy, and he remained alive and in good health without recurrence for more than 5 years. At 5 years and 7 months after gastrectomy, he noticed cervical lymph node swelling and underwent further examination. He was diagnosed with recurrent gastric cancer in cervical lymph nodes, and treatment with S-1 (120 mg/ day) was initiated. He remained alive and free of progression for approximately 1 year on S-1 therapy, but he suddenly died from disseminated intravascular coagulation without an obvious cause. We report a rare case of late recurrence after curative resection in a patient treated for early gastric cancer.

Topics: Biopsy; Combined Modality Therapy; Disseminated Intravascular Coagulation; Drug Combinations; Fatal Outcome; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur; Time Factors

We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.. Among MGC patients (n=108), who received S-1 (40 mg m(-2) b.i.d., days 1-14) and cisplatin (60 mg m(-2), day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487).. Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3%; P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death.. Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Cisplatin; Cytochrome P-450 CYP2A6; DNA-Binding Proteins; Drug Combinations; Endonucleases; Female; Genotype; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Tegafur; X-ray Repair Cross Complementing Protein 1

We retrospectively examined patients with advanced gastric cancer who underwent S-1/CDDP combined neoadjuvant chemotherapy. Nine patients who had the factor of curative surgery deemed not feasible for advanced gastric cancer were enrolled. 80 mg/m2 of S-1 was given orally from days 1-14, and 60 mg/m2 of CDDP was administered on day 8. Patients were treated with a three-cycle protocol. When an adverse event greater than Grade 3 showed, we judged that chemotherapy could not be continued and surgery was performed. An anti-tumor effect on the imaging was found in all cases of PR. The histological effect was judged to be Grade 3 and pathological CR in two cases. In the postoperative period, all patients received adjuvant chemotherapy. S-1/CDDP combined neoadjuvant chemotherapy is a potential regimen for advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

When treating advanced and metastatic breast cancer patients with chemotherapy, it is mandatory to maintain the patients quality of life while keeping an acceptable level of antitumor activity. For these purposes, oral administration of S-1, fluorinated pyrimidine, is a good choice of treatment. Conventionally, a 4-week administration followed by a 2-week rest has been the treatment of choice with S-1. However, we applied a new regimen for 16 patients with advanced and metastatic breast cancer, in which one course consisted of a 2 week-administration followed by a week of rest, repeated twice. The median age of the patients who received this treatment was 59 years old(range 46. 8-80. 6). The response rate was 31. 2%, and the median values of time to progression and overall survival were 5. 1 and 17. 9 months, respectively. One case of thrombocytopenia as an adverse event was recognized. Our new S-1 regimen is likely to show an acceptable anti-tumor effect with minimal adverse events. The fidings suggest that this new regimen is clinically applicable for advanced and metastatic breast cancer patients.

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Tegafur

S-1, an oral fluoropyrimidine, is one of the standard chemotherapeutic agents for the treatment of metastatic gastric cancer(MGC). However, the most effective second-line regimen after failure of treatment with first-line agents such as S-1 is yet to be determined. The aim of this study was to investigate the various second-line chemotherapy regimens in MGC patients.. We retrospectively studied patients with MGC who received second-line treatment after failure of the first-line S-1 or S-1/cisplatin treatment. The overall survival times with each second-line regimen were determined using the Kaplan-Meier method, and the effect on overall survival was analyzed using Cox regression analysis.. The median survival time for all patients was 14. 2 months(95% confidence interval(CI): 12. 88-15. 43 months)with a 1-year survival rate of 60. 4%. Kaplan-Meier analysis revealed that the second-line regimens containing irinotecan significantly improved the median survival time as compared to regimens without irinotecan(median survival time: 16. 5 and 13. 8 months, respectively). Cox regression analysis showed that irinotecan-containing regimens were associated with improved overall survival(hazard ratio: 0. 165; 95% CI: 0. 041-0. 665).. The use of irinotecan-containing regimens as second-line chemotherapy after failure of first-line S-1 therapy may be beneficial for MGC patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Male; Neoplasm Metastasis; Oxonic Acid; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Tegafur

Combination of docetaxel, cisplatin, and S-1 (DCS) is expected as a new treatment regimen for far advanced gastric cancer. We performed DCS chemotherapy for six patients, including four cases with invasion to pancreas, three cases with para-aortic lymph node metastasis, and two cases with liver metastasis. Clinical stages were either IIIC or IV for all of the patients. The patients received 2-4 courses of docetaxel (40 mg/m²) and cisplatin (60 mg/m²) on day 1, and S-1 (80 mg/m²) on days 1-14 every 4 weeks. The response rate was 83% (5 PR and 1 SD), and the disease control rate was 100%. Grade 3/4 neutropenia, grade 3 febrile neutropenia, and grade 3 diarrhea were observed in three cases (50%), one case (17%), and one case (17%), respectively. Four of six patients underwent R0 surgery after DCS chemotherapy, and no severe complication was occurred. Histological responses were Grade 2 for two cases, Grade 1b for one case, and Grade 1a for one case, respectively. DCS regimen showed a high objective tumor response, and also is one of the promising regimens as neoadjuvant setting for far advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Combinations; Drug Therapy, Combination; Fluorouracil; Humans; Irinotecan; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur

We performed a single-institution retrospective study to evaluate the efficacy and toxicities of combination therapy with docetaxel and S-1 in patients with advanced or recurrent gastric cancer.. Eighty-six patients with advanced or recurrent gastric cancer were enrolled. Patients received docetaxel, 40 mg/m2, on day 1 and oral S-1, 80 mg/m2/day, on days 1 to 14 every 3 weeks.. All 84 patients were assessable for response. The overall response rate was 52.4% (44/84) and the disease control rate was 96.4% (81/84). Median time to progression (TTP) and overall survival (OS) were 6.5 (95% CI, 4.8-8.1 months) and 15.1 months (95% CI, 11.7-18.5 months), respectively. The major toxicities were neutropenia, leukopenia, alopecia and anorexia. Grade 3 or 4 hematologic toxicities included neutropenia in 31 patients (36.0%), leukopenia in 27 (31.7%), febrile neutropenia in four (4.7%), and anemia in one (1.2%). Other grade 3 toxicities included anorexia in five patients (5.8%), and stomatitis, diarrhea and nausea in one each (1.2%). There was one treatment-related death (1.2%).. The combination of docetaxel and S-1 had good clinical activity with acceptable toxicity in patients with advanced or recurrent gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

We experienced 3 cases of recurrent breast cancer treated with S-1 therapy, delaying tumor progression and improving their quality of life (QOL). All the patients had been previously treated with both anthracyclines and/or taxanes prior to S-1 chemotherapy. All patients almost completed the full dose through the whole course of treatment, and the drug showed good tolerability. Long-term(more than 12 weeks)therapeutic efficacy and the patients' QOL have been maintained for all patients. No major side effects were seen. It is thought that less toxicity enabled patient 3 to undergo long-term therapy. It is especially important that one patient had therapeutic efficacy and QOL improvement from treatment with S-1 and aromatase inhibitor for over 3 years, after being treated with anthracyclines, taxanes and vinorelbine. We conclude that S-1 is effective and well tolerated in patients with metastatic breast cancer, and will accommodate a long-time progression with respect to efficacy and maintaining the patients' QOL. Further evaluation of S-1 is necessary to elucidate its clinical role in breast cancer treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 7 0-year-old female underwent distal gastrectomy for gastric cancer in November 2001. She did not wish to receive postoperative adjuvant chemotherapy. In May 2002, her serum carcinoembryonic antigen(CEA)level rose. CT demonstrated liver(S5/6)and lung(S9)metastases in August 2002. We started to treat her with S-1(100mg/day day 1-14 orally), and restaging CT showed complete regression of liver and lung metastases in August 2003. In spite her complete response(CR), we continued S-1 treatment for the successive two years. No adverse reaction to chemotherapy occurred. Although CR was maintained for about 4 years, she was found to have a 9-mm solitary lesion in the upper pole of the spleen in June 2007. After 6 months, this tumor increased to 15mm in size, and we considered it as a solitary metastasis to the spleen from gastric cancer. S-1 chemotherapy was restarted, but tumor size gradually increased. Tumor size finally reached 25mm in December 2008. She underwent splenectomy in January 2009. From then until now, she has not received any chemotherapy, and has been followed well without any recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Female; Gastroenterostomy; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Oxonic Acid; Remission Induction; Splenectomy; Splenic Neoplasms; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

S-1, an oral fluoropyrimidine derivative, has been identified as an effective agent for the treatment of breast cancer. We present here a case of interstitial pneumonitis that occurred after S-1 treatment. A n 80-year-old woman was diagnosed with stage III infiltrating ductal carcinoma of the left breast and underwent a modified radical mastectomy in November 2001, followed by six courses of paclitaxel. In October 2008, metastatic disease was detected in her skeletal system. Therefore, S-1 chemotherapy was initiated (100 mg/body). Five days after starting S-1, she developed severe eruptions along with dyspnea. X-rays and CT scan showed diffuse ground glass shadow. Both her symptoms and the radiographic findings resolved dramatically after the start of high-dose corticosteroid therapy. Clinicians should be aware that S-1 has the potential to cause lung injury when it is included in chemotherapy.

Topics: Aged, 80 and over; Breast Neoplasms; Drug Combinations; Female; Humans; Lung Diseases, Interstitial; Neoplasm Metastasis; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

The outcome of stage III gastric cancer patients treated by D2 dissection followed by adjuvant chemotherapy with S-1 remains unsatisfactory. Moreover, some patients with a preoperative diagnosis of stage II/III turn out to be stage IV after surgical exploration, and a standard postoperative treatment for this population has not been established.. A feasibility study of postoperative S-1/cisplatin (CDDP) was performed with patients who underwent gastrectomy for what turned out to be a stage IV gastric cancer. The primary endpoint of the trial was the relative dose intensity during five courses of S-1/CDDP. Several criteria to skip, postpone, or reduce the dose had been predetermined.. Between 2007 and 2009, 31 patients were accrued, including 19 patients who were positive for peritoneal washing cytology, 6 with peritoneal seeding, 5 with metastasis to the paraaortic nodes, and 4 with other distant metastases. Only 7 patients completed five cycles as planned (median, two cycles). The median relative dose intensities of S-1 and CDDP were 37% and 40%, respectively. Causes of treatment failure were failure to fulfill criteria for starting a new course within 5 weeks of the last administration of S-1 in 7, patient refusal in 6, disease recurrence/progression in 4, need to reduce dose by two levels in 4, and two successive skips of CDDP in 3 patients. The median progression-free survival time of all patients was 363 days.. Although promising in the neoadjuvant and advanced/metastatic setting, S-1/CDDP is too toxic as a postgastrectomy treatment for Japanese patients.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Japan; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Postoperative Care; Stomach Neoplasms; Survival Analysis; Tegafur; Time Factors; Treatment Outcome

S-1 is an orally administered fluorinated pyrimidine with high activity in metastatic breast carcinoma (MBC) and in chemotherapy-pretreated metastatic breast carcinoma.. Forty patients with MBC who did not respond to capecitabine-based chemo-therapy and then received S-1 were identified from our data base of records between 2006 and 2008. The clinico-pathological data and outcomes of these patients were then reviewed.. The overall response rate was 27.8%. The median survival was 19.2 months, and the median time to disease progression was 6.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (15%), nausea (15%), vomiting (7.5%), disorder of taste (7.5%), and diarrhea (5%). However, the majority were mild to moderate in intensity, and only one patient experienced grade 3 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths.. The results of the current study demonstrate that S-1 is an effective and well-tolerated treatment in patients with capecitabine-resistant MBC. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Capecitabine; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Retrospective Studies; Salvage Therapy; Tegafur; Treatment Outcome

Thymic carcinoma is a rare intrathoracic malignant tumor, and the prognosis for patients with advanced stage of the disease is poor. However, no definitive chemotherapeutic regimen has been established for advanced thymic carcinoma in front-line settings. The efficacy and benefit of second-line or salvage chemotherapy are also unknown, as few cases or case series have been reported.. We evaluated the efficacy and toxicity of S-1 monotherapy with S-1, a novel oral fluoropyrimidine agent, as salvage therapy in four consecutive patients with previously treated advanced thymic carcinoma from January, 2008 to May, 2010.. Two patients achieved stable disease, and two achieved partial response. Median progression-free survival was 8.1 months. Hematological toxicity was mild, but gastrointestinal toxicity led to discontinuation in two of four patients.. We concluded that oral S-1 monotherapy is useful as second-line or later chemotherapy in previously treated patients with advanced thymic carcinoma and is a potential alternative choice for patients who cannot tolerate platinum-containing treatments.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma; Disease Progression; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Salvage Therapy; Tegafur; Thymus Neoplasms

We report a case of multi-drug-resistant breast cancer with liver metastases which completely responded and improved the quality of life (QOL)by S-1 monotherapy. The patient was a 53-year-old woman, who was diagnosed as breast cancer with invasive chest wall, cervical lymph node metastases, multiple bone metastases and bilateral pleural effusion[invasive ductal carcinoma, scirrhous type, ER(-), PgR(+), HER2(1+)]. After six courses of cyclophosphamide+epirubicin(CE)and weekly paclitaxel for 3 months, cervical lymph node metastasis was judged as a partial response(PR)and the bilateral pleural effusion disappeared. After chemotherapy, aromatase inhibitor (AI) was used. However, primary lesion and multiple bone metastases no change(NC). Following pass through AI+ oral anticancer drug combination chemotherapy and oral anticancer drug monotherapy, the therapy was changed to palliative, and she was referred to our hospital in January 2007. On arrival at the hospital, respiratory distress and bilateral pleural effusion had appeared, so it was an emergency admission. After removing the pleural effusion, pleurodesis was done and the symptoms disappeared. Although AI plus bisphosphonate therapy were started at hospital discharge, disease progression and fatigue appeared. In December 2007, we started S-1 monotherapy. S-1 was given orally at 80 mg/m2 for day 1-28 followed by a 2-week rest period, within a 6-week courses. Six months after treatment was started, multiple liver metastases disappeared and peritoneal effusion decreased. During the period of S-1 treatment, there were no serious adverse events, and treatment was possible without compromising QOL. This result suggested that S-1 treatment was a reasonable option for multi-drug-resistant breast cancer.

Topics: Antimetabolites, Antineoplastic; Breast Neoplasms; Carcinoma, Ductal, Breast; Drug Combinations; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur

We experienced a case of triple-negative recurrent breast carcinoma achieving a significant improvement by oral S- 1, a fluoropyrimidine-class anticancer drug and zoledronic acid(ZOL), a third generation bisphosphonate(BP). / Against metastases to orbital foramen, chest wall and bone, the oral treatment with S-1 was started at 80 mg/day everyday for 4 weeks, followed by a 2-week rest interval as 1 cycle, and ZOL was injected at 4 mg every 4 weeks. After 2 cycles of treatment, the level of tumor markers and tumor sizes became reduced. Twelve cycles after the initiation of the therapy, recrudescence of the metastatic lesions was not recognized, and no other metastases were recognized in any organ. In the course of the treatment, no adverse drug reactions to S-1 occurred in the patient. For treatment of recurrent breast carcinoma, S-1 is considered to be a useful and tolerable anticancer drug, and combination treatment of S-1 and ZOL is thought to be effective.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Diphosphonates; Drug Combinations; Female; Humans; Imidazoles; Magnetic Resonance Imaging; Neoplasm Metastasis; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed; Treatment Outcome; Zoledronic Acid

Chemotherapy with irinotecan (CPT-11) or oxaliplatin (l-OHP) in combination with infusional 5-fluorouracil (5-FU) and their cross-over as second-line therapies are standard treatments for metastatic colorectal cancer (MCRC). Molecular target agents, which are used as third-line therapies in Western countries after failure of these three drugs, have not been available in Japan. Monotherapy with S-1 [Tegafur, Oteracil potassium and 5-chloro-2,4-dihydroxypyrimidine (CDHP)] showed activity against colorectal cancer with a response rate of 35% as a first-line therapy. It is not clear whether inhibition of dihydropyrimidine dehydrogenase by CDHP can modulate the activity of 5-FU even after patients initially fail with 5-FU. This retrospective study evaluated the efficacy and safety of monotherapy with S-1 for MCRC after the failure of standard chemotherapy.. The subjects of this study comprised two cohorts; the first was 27 patients with MCRC who had failed with 5-FU and CPT-11 before approval of l-OHP in Japan (cohort 1), and the second was 23 patients who had failed with 5-FU, CPT-11 and l-OHP (cohort 2). S-1 was given orally twice daily (80 mg m(2)/day) for 28 days followed by a 14-day rest.. In cohorts 1 and 2, the response rates were 7% and 0%, and the median progression-free survivals were 2.8 and 2.7 months, and overall survivals after initiation of S-1 were 10.5 and 4.7 months, respectively. The common grade 3 and 4 adverse events in cohorts 1 and 2 were diarrhea 15% and 13%, anorexia 11% and 17% and anemia 26% and 30%, respectively.. S-1 monotherapy did not show promising activity against MCRC after the failures with 5-FU, CPT-11 and l-OHP.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pyrimidines; Retrospective Studies; Tegafur

Case one was a 76-year-old woman. She was diagnosed as having lung adenocarcinoma with multiple metastases (cT4N0M1, stage IV, mucinous BAC)in June, 2004. Starting in July, 2004, she received various modalities of chemotherapy( cisplatin+vinorelbine, gefitinib, pemetrexed, gemcitabine, docetaxel, paclitaxel). S-1 monotherapy given to her starting April, 2006 achieved a partial response(PR)as a seventh-line treatment. Case two was a 60-year-old woman. She was diagnosed as having lung adenocarcinoma with multiple metastases(cT4N3M1, stage IV)in October, 2004. That month, her chemotherapy began. After various treatments(cisplatin+vinorelbine, docetaxel, gefitinib), S-1 monotherapy was initiated in February, 2007 as the fourth-line treatment; as a result, PR was achieved. Even though chemotherapies were performed in succession, in the condition of good general status, salvage chemotherapy can be affected by the rotation of drugs. In such cases, S-1 monotherapy can be a reasonable choice from the standpoint of feasibility and effectiveness.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Combinations; Fatal Outcome; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Radiography; Recurrence; Salvage Therapy; Tegafur; Treatment Outcome

A 72-year-old female patient with type 5 gastric cancer in the upper gastric region underwent surgery. Due to paraaortic lymph node metastasis (#16a1, #16a2) and peritoneal metastasis, total gastrectomy and D0 lymph node dissection were performed. Surgical and pathological findings were poorly differentiated adenocarcinoma, INFbeta, pT3(SE), PM (-), DM (-), ly0, v2, sN3 (#7, #9, #16a1-a2), M0, stage IV. The patient was administered S-1 for 2 weeks at 80 mg/day, received 24-hour continuous intravenous infusion of 80 mg/day on day 8, and then discontinued chemotherapy for 2 weeks, which was regarded as one course. After one course, CT scan showed that the paraaortic lymph node metastasis had almost entirely disappeared. However, due to grade 3 neutropenia, and grade 2 nausea and anorexia in the first course, the treatment was changed to oral administration of UFT (400 mg/day) , which was discontinued one month later due to anorexia. The patient has been in good health without a recurrence for 4 years after surgery. This case suggests that reduction surgery combined with a S-1 regimen is an effective treatment for long-term survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

The 3-drug regimen of CPT-11+5-FU+l-LV is generally used for metastatic and/or recurrent colorectal cancer. We have applied this treatment as the first-line intervention in our hospital. However,when the efficacy is reduced we try chemotherapy using CPT-11+TS-1 for 5 outpatients as second- or third-line chemotherapy. Decreased CEA levels were subsequently observed in 4 of 5 cases. In addition, 2 cases exhibited grade 1 or 2 adverse effects, but no case developed neutropenia. We could expect such effects even for patients after only 5-FU, and this treatment may be performed safely on ambulatory patients.

Topics: Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur

We investigated the clinical efficacy and safety of S-1 retrospectively for the treatment of 32 patients with advanced gastric cancer after reduction surgery (gastrectomy). S-1 was administered orally twice daily, at a standard dose of 80 mg/m(2) per day for 28 days, followed by a 14-day rest. There were 21 patients having only a single residual metastatic site and 11 with two or more metastatic sites. Major residual metastatic sites were peritoneum in 25 patients, lymph nodes in 7, liver in 4 and lung in 2. The response rate by target organ was 28.6% for lymph node metastasis, and 0% for liver and lung metastasis. Peritoneal metastasis was not considered measurable site. The median survival time (MST) after S-1 administration was 573 days (95% confidence interval, 439 to 707 days). The 1-, 2- and 3-year survival rates were 62.3%, 40.3% and 28.2%, respectively. Of the 32 patients, 14 received S-1 for more than a year, and the MST in these patients was 897 days (95% confidence interval, 255 to 1,539 days). The incidence of adverse events was 90.6%, but the incidence of grade 3 or 4 was 12.5%. Long-term administration of S-1 may serve to prolong the survival period of patients with gastric cancer after reduction surgery, particularly in peritoneal metastasis.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

S-1, an oral fluoropyrimidine, has been shown to have excellent activity against gastric cancer in two phase II studies and is widely used in Japan. However, the long-term outcomes of patients after S-1 monotherapy for metastatic gastric cancer are unclear. The aim of this study was to investigate the long-term outcomes in metastatic gastric cancer patients who had initially received S-1 monotherapy.. Ninety-two previously untreated patients with advanced gastric cancer received S-1 monotherapy as first-line chemotherapy at the National Cancer Center Hospital East, Kashiwa, Japan, and then the long-term outcomes and characteristics of long-term survivors were analyzed retrospectively. Multivariate analysis of prognostic factors was performed by the Cox proportional hazard method.. With a median follow-up of 3.1 years, the median progression-free survival time was 4.6 months. The median survival time was 11.9 months, with 1-, 2- and 3-year survival rates of 49.1%, 22.8%, and 9.8%, respectively. Multivariate analysis showed that good performance status (P = 0.0004) and only one metastatic site (P = 0.0048) were significant independent prognostic factors. Among 48 patients with a single metastatic site, 22 with peritoneal metastasis had longer survival times (median survival, 24 months) than patients with metastasis at other sites. Among the nine 3-year survivors, six had peritoneal metastases alone.. The survival outcomes after S-1 monotherapy are promising, especially in patients with good performance status and a single metastatic site. Our findings suggest that, among patients with a single metastatic site, those with peritoneal metastases alone have a chance for long-term survival.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Humans; Japan; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

We evaluated the expression of 5-FU pathway genes in prechemotherapeutic fresh frozen samples obtained from primary tumors to predict response and survival of 59 metastatic gastric cancer patients treated with S-1 monotherapy as first line treatment. Five 5-FU pathway genes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP) and uridine phosphorylase (UP), were analyzed by the quantitative real-time reverse transcriptional PCR method. Median values of each gene were selected for cut-off values separating high and low gene expressions. In univariate analyses, low TS, high OPRT and low TP were significantly associated with a tumor shrinkage and a long survival, whereas DPD and UP gene expressions did not correlate with response and survival. Multivariate analyses revealed that independent variables were OPRT and TS for response and TS and TP for survival. When OPRT and TS were combined, a significantly increased accuracy rate of 91.5% was seen for response. Similarly, an increased hazard ratio of 10.29 was observed for survival in patients possessing low TS and low TP, compared with those with high TS or high TP. The simple combinations of 2 genes, OPRT and TS for response and TS and TP for survival, may allow identification of gastric cancer patients who will benefit from S-1 chemotherapy.

Topics: Adult; Aged; Drug Combinations; Drug Therapy, Combination; Female; Fluorouracil; Gene Expression; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

A 55-year-old-male patient underwent subtotal esophagectomy for esophageal cancer (pT1b, N0, M0, stage II) in April 2005. The patient received postoperative chemotherapy (docetaxel 40 mg/body, 5-fluorouracil 750 mg/body, cisplatin 10mg/body: administered every 4 weeks) for 3 months. Six months postoperatively, routine follow up CT demonstrated multiple metastatic tumors in the bilateral lungs. Under the diagnosis of multiple lung metastases, the patient was hospitalized and received intensive chemotherapy with docetaxel 40 mg/week (day 1), 5-fluorouracil 500 mg/day (days 1-5), cisplatin 10 mg/day (days 1-5). After two weeks administration, the patient eagerly hoped for outpatient treatment. The treatment was changed to outpatient chemotherapy with S-1 100 mg/day (continuous administration for 3 weeks followed by rest for 1 week) and cisplatin 20 mg/every week. The treatment enabled the patient to keep working. Follow up CT showed disappearance of all tumors two months after TS-1/cisplatin chemotherapy. There were no obvious signs of recurrence 5 months after chemotherapy. The S-1/cisplatin therapy in the outpatient was thought to be one of the effective treatments in maintaining quality of life for the patient.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Fluorouracil; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Recurrence; Taxoids; Tegafur

To evaluate the antitumor and antimetastatic efficacy of oral fluoropyrimidines, alone and combined with taxane on human breast cancer xenografts model, we developed a breast cancer model that spontaneously metastasizes to the lung by orthotopic implantation of MDA-MB-435S-HM tumors into the mammary fat pad (mfp) of SCID mice. The activity of the 5-fluorouracil (5-FU)-degrading enzyme dihydropyrimidine dehydrogenase (DPD) was significantly higher in the metastatic tumors than in the primary tumors. Based on this enzymatic characteristic of pulmonary metastases of breast cancer in regard to 5-FU metabolism, we investigated the antitumor activity of two types of oral 5-FU prodrugs, with and without paclitaxel, on both orthotopically implanted breast tumors and metastatic lung tumors in mice. The drugs and doses used were: S-1, a new oral DPD-inhibiting fluoropyrimidine (DIF) 8.3 mg/kg/day, capecitabine 360 mg/kg/day as a non-DIF, and paclitaxel 50 mg/kg, all of which display minimal toxicity in mice. In the primary tumors, paclitaxel and S-1 displayed a significant antitumor activity, with 57 and 41%, respectively inhibition of tumor growth (p < 0.01), but capecitabine had no effect. When S-1 and paclitaxel were combined, they synergistically caused tumor regression (tumor growth inhibition ratio 94%, p < 0.01) in mice compared to capecitabine plus paclitaxel, without any toxicity. In the pulmonary metastasis model, paclitaxel, and both S-1 alone and combined with paclitaxel, but not capecitabine alone or combined with paclitaxel, diaplayed almost complete antimetastatic activity. These results strongly suggest that combination of S-1, as a DIF with taxanes will show a potent high antitumor and antimetastatic effect on refractory human breast cancers, especially those expressing strong DPD activity.

Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Disease Models, Animal; Drug Combinations; Female; Mice; Mice, SCID; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Pyridines; Tegafur; Transplantation, Heterologous

A 67-year-old woman with anorexia and weight loss was referred to our hospital with a diagnosis of type 4 gastric cancer. Since metastases to the liver, left adrenal gland, and Douglas' pouch were detected in addition to ascites and bilateral hydronephrosis, the tumor was judged unresectable and systemic chemotherapy with TS-1 was begun. Symptoms began to improve after the first course, and the patient was discharged and followed as an outpatient. An upper GI series showed improvement of the primary lesion, and cancer cells became undetectable under biopsy. At the end of the third course, computed tomography confirmed that metastases to the liver, the lymph nodes, and the adrenal gland had disappeared. The ascites diminished significantly, and hydronephrosis began to ameliorate. The effectiveness of the drug continued until the end of the eleventh course, and the patient is currently in her seventeenth month as an outpatient. This case shows the effectiveness of TS-1 against scirrhous type gastric cancer, a cancer generally considered resistant to chemotherapy. Furthermore, treatment on an outpatient basis has greatly improved her quality of life.

Topics: Adenocarcinoma, Scirrhous; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Fluorouracil; Humans; Neoplasm Metastasis; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Colonic Neoplasms; Drug Combinations; Fluorouracil; Humans; Neoplasm Metastasis; Neoplasm Transplantation; Oxonic Acid; Prodrugs; Pyridines; Rats; Rats, Nude; RNA; Tegafur; Transplantation, Heterologous